<SEC-DOCUMENT>0000874015-21-000074.txt : 20210505
<SEC-HEADER>0000874015-21-000074.hdr.sgml : 20210505
<ACCEPTANCE-DATETIME>20210505145830
ACCESSION NUMBER:		0000874015-21-000074
CONFORMED SUBMISSION TYPE:	10-Q
PUBLIC DOCUMENT COUNT:		59
CONFORMED PERIOD OF REPORT:	20210331
FILED AS OF DATE:		20210505
DATE AS OF CHANGE:		20210505

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-Q
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		21892768

	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-Q
<SEQUENCE>1
<FILENAME>form10q.htm
<DESCRIPTION>IONIS PHARMACEUTICALS INC 10-Q 3-31-2021
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;"><hr style="border: none; border-bottom: 1px solid black; border-top: 4px solid black; height: 10px; color: #ffffff; background-color: #ffffff; text-align: center; margin-left: auto; margin-right: auto;" />UNITED STATES</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;"><!--PROfilePageNumberReset%Num%1%%%-->SECURITIES AND EXCHANGE COMMISSION</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Washington, DC 20549</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Mark One)</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">OR</div>
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<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">For the transition period from _____ to _____</div>
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<div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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<div><br /></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>
<table cellpadding="0" cellspacing="0" id="zf24f228ede6f4e2d9dd8acacdcc4dea9" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
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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;">Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted and posted 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_cf867d5504894c60a8672f78f2846229" contextRef="c20210101to20210331">Yes</ix:nonNumeric>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#x2612;</span> No <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#x2610;</span></div>
<div><br /></div>
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    <td style="width: 50%; vertical-align: top;">&#160;</td>
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  <tr>
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  <tr>
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<div><br /></div>
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<div><br /></div>
<div>
<div><br /></div>
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<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
<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><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><!--PROfilePageNumberReset%Num%2%%%-->IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FORM 10-Q</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX</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="zed3ddf89b7de446bb8ac715c80366665">
  <tr>
    <td style="width: 9.88%; 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 I</div></td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FINANCIAL INFORMATION</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 9.88%; 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: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial Statements:</div></td>
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  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Balance Sheets as of March 31, 2021 and December 31, 2020 (unaudited) (as revised)</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
  </tr>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Operations for the three months ended&#xA0;March 31, 2021 and 2020 (unaudited) (as revised)</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div></td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Comprehensive Loss for the three months ended&#xA0;March 31, 2021 and 2020 (unaudited) (as revised)</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div></td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Stockholders&#8217; Equity for the three months ended&#xA0;March 31, 2021 and 2020 (unaudited) (as revised)</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6</div></td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Cash Flows for the three months ended&#xA0;March 31, 2021 and 2020 (unaudited) (as revised)</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div></td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Notes to Condensed Consolidated Financial Statements (unaudited)</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div></td>
  </tr>
  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
  </tr>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 2:</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
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    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Results of Operations</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liquidity and Capital Resources</div></td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38</div></td>
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  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 4:</div></td>
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    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; 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>
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    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 1A:</div></td>
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    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56</div></td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; 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>
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    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 7.92%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 5:</div></td>
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    <td style="width: 7.92%; vertical-align: bottom; background-color: #CCEEFF;"><div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56</div></td>
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    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 9.88%; 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>
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    <td style="width: 82.21%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">TRADEMARKS</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;&#8220;</span>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 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>2</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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<div><br /></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;">CONDENSED CONSOLIDATED BALANCE SHEETS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in thousands, except share data)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z94ae6fd80c9549b7a18448e6249c228a" 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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  <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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    <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="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="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>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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>
  </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>
  </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; 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="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_552968f4f2a9496e83f175a2ee89b95c" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">29,263</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>
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  </tr>
  <tr>
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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>
    <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="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_bfee8ed3f29a415ba60a766b5e0cc4b7" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,688</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_41e0bc055640457ebe9012a9d8313b03" contextRef="c20201231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,301</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: 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_09d676ed2f6648e5b73076a656df1277" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">106,740</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_0b483c68b6994735bd21436d4b811df6" contextRef="c20201231" unitRef="U002" 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>
  </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 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_b563c92d4e8b4add87b63f57c52a0e82" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">295,105</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_d521a592d7c446a7b398adb17b375e32" contextRef="c20201231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">598,898</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%;">&#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_8aa6408241e44715ba99551864adcae8" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">401,966</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_ede8dfed22c34e9582c277c64ee5a671" contextRef="c20201231" unitRef="U002" 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>
  </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_714a80b1e06f495582600aaf17011943" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">540,679</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_28e26d3aa3364b35803b96f04b984592" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">540,136</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_bbd023eee50e42438aa37192e3fb599a" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_3d6e1ab8d0ea4dfca582273a77b28bd5" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction></ix:nonFraction> percent convertible senior notes, 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:ConvertibleDebtNoncurrent" id="Fact_bc21a6be6e71486ba7dfcbdbdb6f2f71" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">247,292</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_b04f36c3d9184527845604b604aab2e1" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8211;</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_fd5cf7d013b54a0388cfec028fd6a1c3" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">22,943</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_54d2771a1e14483ab99a8f4e34dd5224" contextRef="c20201231" unitRef="U002" 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>
  </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;">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_5af98209ca0a49319c15718880999db5" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">60,002</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_b3ea6b13b4de4225adb6586558c16a06" contextRef="c20201231" unitRef="U002" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 54pt; 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_b675286a500340028e4203fe4698ca8a" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,567,987</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; 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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    <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>
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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: 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>
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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_ce487df6de7f42f7b8c77a08d145dc67" contextRef="c20201231" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">21,071</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;">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>
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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%; 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;">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:StockholdersEquity" id="Fact_88e09c1d71dc4fa5bb36f4591af70f7e" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">680,564</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:StockholdersEquity" id="Fact_54e7a9222a6849019c33f1fa21e47093" contextRef="c20201231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">743,282</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: 54pt; 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>
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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>
    <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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  </tr>
</table>
<div><br /></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="z30916fe6c3bd47a0809d50a9617b07d5">
  <tr>
    <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;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</div></td>
  </tr>
</table>
<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;"><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><br /></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;">CONDENSED 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 style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zb6d529abe5f74f76ac782b0ae7b7264d" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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;">&#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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(as revised*)</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: 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td 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; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div></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%; 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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  <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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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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>
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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>
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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:CostOfGoodsAndServicesSold" id="Fact_4149679d19a344ec8f07f14a2a4514d5" contextRef="c20210101to20210331" unitRef="U002" 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:CostOfGoodsAndServicesSold" id="Fact_68ba2fda58a44024be5ff63f94e807d0" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,548</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%;">&#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="ions:ResearchDevelopmentAndPatentExpense" id="Fact_8fb85da59dd6434798e0931699f46727" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">139,801</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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  </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>
    <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:SellingGeneralAndAdministrativeExpense" id="Fact_061c029e7dfc4b68ae21550ce885f82a" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">61,199</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:SellingGeneralAndAdministrativeExpense" id="Fact_7f9fe47be1834daca6afdaa55e9445df" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">74,994</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: 27pt; 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: 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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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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>
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    <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; text-align: right; width: 9%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#160;</td>
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    <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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  <tr>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#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>
    <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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<div><br /></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="z4fea89aa8b1b4d2daa7159d5eeff659a">
  <tr>
    <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;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</div></td>
  </tr>
</table>
<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;"><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>
</div>
<div><br /></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;">CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zee68b052ab06476ab957bb5fabb4806f" 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="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; 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="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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(as revised*)</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: bottom;">&#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>
    <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>
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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>
    <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;">Currency translation adjustment</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>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#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: 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;">Comprehensive loss</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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  <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>
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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>
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  <tr>
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  </tr>
</table>
<div><br /></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="z68bad09d728f44309ee86a0589af7eb9">
  <tr>
    <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;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</div></td>
  </tr>
</table>
<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;"><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><br /></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;">CONDENSED 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;">Three Months Ended&#xA0;March 31, 2020 and 2021</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</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="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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    <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%; 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>
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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="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="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%;">&#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%; 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>
    <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>
    <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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3d90fbbf5e5e4552969a2652859120f1" contextRef="c20200101to20200331_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_abe5472affc54cdc9a4597cd351df2b5" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">40,790</ix:nonFraction></div></td>
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  </tr>
  <tr>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 4px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at March 31, 2020 (as revised*)</div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 20%; 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>
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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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    <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%; 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: 20%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at March 31, 2021</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;">&#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>
    <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_0fa1ab6fe60a48e88125f45695548614" contextRef="c20210331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">141</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_ba66578036484b5f968843707bc07ed1" contextRef="c20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,925,801</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 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_459e8dddf67049ffbc89a031afcfb160" contextRef="c20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">24,203</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;">&#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>
    <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_5da31e271bbc4395b26f5d34fd4e692d" contextRef="c20210331_StatementEquityComponentsAxis_ParentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">680,564</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_192d6c524908459d8333a666b536f1b0" contextRef="c20210331_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 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_410eb94491b24411ae562ce3bd42c127" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">680,564</ix:nonFraction></div></td>
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  </tr>
</table>
<div><br /></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="z6e467eda53824987a9b53e241326308e">
  <tr>
    <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;">We revised our 2019 and 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</div></td>
  </tr>
</table>
<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;"><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><br /></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;">CONDENSED 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 style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z74997fc50fbb4cd8a057493b360cfc94" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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;">&#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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(as revised*)</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: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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>
  </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;">Net loss</div></td>
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  <tr>
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  <tr>
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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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of patents</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;">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of premium (discount) on investments, net</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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    <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: 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;">Amortization of debt issuance costs</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="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>
    <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;">Stock-based compensation expense</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:ShareBasedCompensation" id="Fact_04aaa2990d5a40ad8fdb1b5232b70a08" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">37,861</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;">Gain on investments</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: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash losses related to patents</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:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_7fcd200b638b455db39131034fdc6876" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">221</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:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_fe5c9b55fb8549bebb24e58da0204a34" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">159</ix:nonFraction></div></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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Provision for deferred income taxes</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:DeferredIncomeTaxExpenseBenefit" id="Fact_8414c778f38f421ba72eccd5272fd411" contextRef="c20210101to20210331" unitRef="U002" 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>
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  <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;">Changes in operating assets and liabilities:</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>
  </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;">Contracts receivable</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:IncreaseDecreaseInContractWithCustomerAsset" id="Fact_16676ffc3ca64894b557287e56466f06" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">52,807</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:IncreaseDecreaseInContractWithCustomerAsset" id="Fact_4adb47def1984cd7bbd6593823908452" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">34,429</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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  <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;">Accounts payable</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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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued 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>
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    <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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    <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: 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;">Accrued liabilities and other current liabilities</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;">&#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: 36pt; 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;">&#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>
    <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: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash used in operating 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:NetCashProvidedByUsedInOperatingActivities" id="Fact_66c31f18a56f439ab964f9bf11cd801d" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">54,662</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:NetCashProvidedByUsedInOperatingActivities" id="Fact_aaaa638d546d45448755c94c63222ccd" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,592</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#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: 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; font-weight: bold;">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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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_083200534ca3433a9d3c58296e5b5402" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">330,051</ix:nonFraction></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>
  <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;">Proceeds from sale of short-term investments</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:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_421423d1ea9a4d73aef63e7e59de4afb" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">411,907</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>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchases of property, plant and equipment</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="text-align: left; vertical-align: bottom; width: 1%;">&#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%; 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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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">&#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>
    <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>
    <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; font-weight: bold;">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>
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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>
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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: 36pt; 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>
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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:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_ddb0c2b46432418f9be1b92d0e804ae9" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,760</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_8bffc0bd215e4f839416df4a6531312e" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,652</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: -9.15pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div></td>
    <td 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_b75a3de029544b8ea1fafba1be80eb98" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,337</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%; 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;">Repurchases and retirements of common stock</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:PaymentsForRepurchaseOfCommonStock" id="Fact_debd829012124436b0de04a28fa90961" contextRef="c20210101to20210331" unitRef="U002" 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:PaymentsForRepurchaseOfCommonStock" id="Fact_54f753502f1e48f180c1bc730693f37d" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">90,550</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash used in financing 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:NetCashProvidedByUsedInFinancingActivities" id="Fact_eaaca3e288be4952adf9a7f8f7bf8f92" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,577</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:NetCashProvidedByUsedInFinancingActivities" id="Fact_af5d9d765265424f939925e68f5a2822" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">94,501</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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>
  </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:EffectOfExchangeRateOnCashAndCashEquivalents" id="Fact_05d7fd45bf434136a2b94742f2dddc94" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">126</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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    <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;">&#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>
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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>
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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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    <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>
    <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;">Amounts accrued for capital and patent expenditures</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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<div><br /></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="zfb8d85f2537f40f1934f6cb1e76028d3">
  <tr>
    <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;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</div></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;"><span>7</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 CONDENSED CONSOLIDATED FINANCIAL STATEMENTS</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2021</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; 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;">We prepared the unaudited interim condensed consolidated financial statements for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on the same basis as the audited financial statements for the year ended </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, with the exception of our retrospective adoption of Accounting Standards Update, or ASU, 2020-06, which simplifies</span> the accounting for convertible debt instruments<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. See Note 2, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Polices</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; font-style: italic;">Convertible Debt, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for details of our adoption of this guidance. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</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 our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;). We formed Akcea in December 2014. </span>In July 2017, Akcea completed an <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">initial public offering, or IPO, which reduced our ownership of Akcea&#8217;s common stock below </span><ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_ec7fb54350ee4762b85ff0ac101ed744" contextRef="c20170731_OwnershipAxis_AkceaTherapeuticsIncMember_RangeAxis_MaximumMember" 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;">.</span>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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>We 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2.&#160; Significant Accounting Policies</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 condensed 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: TEGSEDI and WAYLIVRA revenue, net</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the United States, or U.S., through the first quarter of 2021, we sold TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that took title to TEGSEDI. The 3PL was our sole customer in the U.S. The 3PL then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In Europe, through 2020, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors. In January 2021, we began commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. In April 2021, we expanded our distribution agreement with Sobi to also include commercializing TEGSEDI in North America. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>8</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;">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;">See <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 5, </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 collaborations with substantive changes that occurred in 2021. Additionally, see </span>Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for a summary of each of our material 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;"><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: left;"><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: left; 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: left;"><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: left;"><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: left;"><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: left;"><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_a5d99bad3ce4453ea2bcc34d06e92ad6" contextRef="c20210101to20210331" 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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.</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: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>9</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain. For example, in the fourth quarter of 2020, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_df927636533f42d0b09abafe0eac07cb" contextRef="c20201001to20201231_ProductOrServiceAxis_Ion449Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">20</ix:nonFraction> million milestone payment from AstraZeneca when AstraZeneca initiated a Phase 2b study for ION449, our medicine in development targeting PCSK9 to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION449 was contingent on AstraZeneca initiating a Phase 2b 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.</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: left;"><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;">Next, we allocate the transaction price to each of our performance obligations. When we have to 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. 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.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may engage a third 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:</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: 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: 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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    <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>
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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: 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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    <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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    <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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    <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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    <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;">We recognize revenue in one of two 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.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>
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<div style="text-align: 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;">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.</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: TEGSEDI and WAYLIVRA revenue, 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;">Prior to our distribution agreement with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreement with Sobi we concluded that our performance obligation is to supply finished goods inventory to Sobi. This performance obligation is a series of distinct activities that are substantially the same because we transfer title using the same criteria each time we ship inventory to Sobi. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Additionally, Sobi does not generally have a right of return.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Reserves for TEGSEDI and WAYLIVRA commercial revenue</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Prior to our distribution agreement with Sobi, w</span>e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were 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 reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. 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 TEGSEDI and WAYLIVRA revenue in the corresponding period. See our revenue recognition 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>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA 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;">Under our distribution agreement with Sobi, Sobi is financially responsible for any applicable reserves.</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;">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 develop IONIS-FB-L<sub>Rx</sub> for the treatment of complement-mediated diseases, we received a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_72588160d9344e3d91319fe6a66f7d24" contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> 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 $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_df2e1cb511f24d2a84b6cc2d7d4dc617" contextRef="c20181001to20181231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInOctober2018WithRocheMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">75</ix:nonFraction> million upfront payment using an input method over the estimated period of time we are providing R&amp;D services.</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;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the fourth quarter of 2020, we achieved a $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPriceAdditions" id="Fact_4419a9d643c14dde9c2d40f4d61b0e4c" contextRef="c20201001to20201231_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">7.5</ix:nonFraction> million milestone payment from Biogen when we advanced a target under our 2018 strategic collaboration. 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.</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_873dc72bf08c413b88b5187cbedd61d2" contextRef="c20200701to20200930_ProductOrServiceAxis_Ion464Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">18</ix:nonFraction> million in milestone payments when Biogen initiated a Phase 1/2 trial for ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy. 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.</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;">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 fourth quarter of 2020, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_432ed8399d7347559e4b9fd7f84313ae" contextRef="c20201001to20201231_ProductOrServiceAxis_Ion455Member_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">30</ix:nonFraction> million license fee from AstraZeneca when AstraZeneca licensed ION455, an investigational medicine in development to treat nonalcoholic steatohepatitis, or NASH.</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;">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.</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;">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 sold 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;">For example, 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. As part of the agreement, Bayer paid us a<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_b0a5ed9e0b0d4e29b24c119065c51524" contextRef="c20150501to20150531_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember" unitRef="U002" 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_f85da3614c52436e9a2747089ce8bf2a" contextRef="c20170201to20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U002" 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_76a7435f661f45b28342f251870de7ff" 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_5d22f781b2fa41009a4196e97f84a1e7" contextRef="c20170228_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" unitRef="U002" 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, 2020&#xA0;<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: 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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    <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_c0d9a811936e47c2b113f70412abe1a4" 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: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis. </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 </span><span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3">one quarter</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of billing our partner or customer</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2021, approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_ddb9c9779caa4c7ba7a8628627b81f91" contextRef="c20210101to20210331_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_ThreeSignificantCustomersMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">46.8</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_1a88c8e3635d4a64afd7542090bb8bb4" contextRef="c20210101to20210331" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> significant customers. As of December 31, 2020, approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_2797753f496a4c3a9e250ecbc9db8bec" contextRef="c20200101to20201231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">99.5</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_61c499808edf4f65970284a4fd7b4782" contextRef="c20200101to20201231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> significant customers.</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 condensed consolidated balance sheet.</div>
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<div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet.</span> During the three months ended&#xA0;March 31, 2021 and 2020, we recognized $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_29a96e3cb4bb4440a9a1b2cd97733561" contextRef="c20210101to20210331" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">26.0</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_9b7323eabb394f1aa269712264f74431" contextRef="c20200101to20200331" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">28.0</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 sales 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 sales. </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 condensed 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 March 31, 2021, we held equity investments in <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8037e90f29fb43ae9797ff009a688387" contextRef="c20210331" unitRef="U008" 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_e003aeab75174162b833cf14b3a44106" contextRef="c20210331" unitRef="U008" 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 condensed 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, during the second and fourth quarters of 2020, we revalued our investments in <ix:nonFraction name="ions:NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" id="Fact_1d052d9ce42e45d89c9a5e9b00144f66" contextRef="c20200401to20201231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> 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 $<ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_db63fed8d9ef462ba313eb95dec39cc7" contextRef="c20200401to20200630_FinancialInstrumentAxis_DynacureSasMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">6.3</ix:nonFraction> million gain on our investment in Dynacure, a $<ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_4c7cacc292da45b4b4d1f5ac19e9efcb" contextRef="c20200401to20200630_FinancialInstrumentAxis_SuzhouRiboLifeScienceCoLtdMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">3.0</ix:nonFraction> million gain on our investment in Suzhou-Ribo and a $<ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_70661b1998e04974912c20ed82ebb966" contextRef="c20200401to20200630_FinancialInstrumentAxis_AroBiotherapeuticsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">5.5</ix:nonFraction> million gain on our investment in Aro Biotherapeutics in our condensed consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 condensed 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 March 31, 2021, 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 insignificant amount of inventory write-offs for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021 and 2020<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;">Our inventory consisted of the following (in thousands):</div>
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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 valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div></td>
    <td 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="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;">&#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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<div style="text-align: left;"><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-weight: bold;">Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed 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. 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 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: 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 style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Patent Expenses</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research 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 condensed consolidated balance sheet and we expense them as the services are provided.</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 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. </span>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<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; font-weight: bold;">Income Taxes</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 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 we expect to realize.</div>
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<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_a98a6d07e6c34da2a2f4b3a917bc30a44" continuedAt="Text_a98a6d07e6c34da2a2f4b3a917bc30a45"><ix:continuation id="Text_383bb745bac14fbfbfede03aae10b424196" continuedAt="Text_383bb745bac14fbfbfede03aae10b424197">
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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.</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 assessed our valuation allowance requirements and recorded a valuation allowance 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. We based our determination 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 we expect this 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. We also expect 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 continue to 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: 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; font-weight: bold;">Long-lived 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 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.</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;">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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the </span>U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>15</span></div>
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<div><ix:nonNumeric name="us-gaap:EarningsPerSharePolicyTextBlock" id="Text_d8ae7016e11e44938c278329c28c5334" contextRef="c20210101to20210331" escape="true" continuedAt="Text_7962147e5678409fa37426bbe317e09f1"><ix:continuation id="Text_383bb745bac14fbfbfede03aae10b424208" continuedAt="Text_383bb745bac14fbfbfede03aae10b424209">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss Per Share</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the first quarter of 2021, we computed basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the period. For the first quarter of 2021, we did not have to consider Akcea results separately in our calculation because we owned <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_13943e6576ca415a83b7d65c86a49bff" contextRef="c20210331_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction> percent of Akcea for the entire period. Our basic net loss per share for the three months ended March 31, 2021 was $<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_aab817918ee7462eafc4e0247e0ea5c8" contextRef="c20210101to20210331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.64</ix:nonFraction>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the first quarter of 2020, prior to the Akcea Acquisition, we calculated our net loss for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period to determine our total net loss attributable to our common stockholders. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s net loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share is different than our net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the three months ended March 31, 2020, was calculated as follows (in thousands, except per share amounts):</div>
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<table cellpadding="0" cellspacing="0" id="z7b5bf2df83804d43854b69383ccbe9b3" 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 solid 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended March 31, 2020</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;">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" 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;">Akcea&#8217;s</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" 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;">Basic</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss Per</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Share Calculation</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(as revised*)</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: top; 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;">Ionis&#8217; portion of Akcea&#8217;s net loss</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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:WeightedAverageNumberOfSharesOwnedInSubsidiary" id="Fact_35767e855cbf450cb21d26c324a1d927" contextRef="c20200101to20200331_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">77,095</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;"><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%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_5e959d88aa6c46ca89a333d0d6cd3637" contextRef="c20200101to20200331_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.42</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:NetIncomeLoss" id="Fact_b5a98a2a39f941be9021fd6378d498c6" contextRef="c20200101to20200331_OwnershipAxis_AkceaTherapeuticsIncMember_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,674</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%;"><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" 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%;"><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:NetIncomeLoss" id="Fact_b3c04982056e46bb89fc30c57b93d79c" contextRef="c20200101to20200331_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,674</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>
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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;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;">&#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;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;">&#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;">&#160;</td>
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    <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>
    <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 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;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</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;">Diluted 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;">For the three months ended&#xA0;March 31, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</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="ze05c20ab8a7a49e99cfabe0891503ad7">
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_eccc4161cecb4e0e9bd2f79ccde27795" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction> percent convertible senior notes;</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="z36c843a3550d4b3e93b2ee38a231b0da">
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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>
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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="z6a7fb101db7048108b6a191da4379108">
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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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_85a6f8e5d22944cab33b8c94b685e2ff" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> percent convertible senior notes;</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="z153e5c3b8aac48fe89e372bb8d6e7bfe">
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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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</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="ze058b3b556b740b1ba0eec702d6ac87b">
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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;">Unvested performance restricted stock units, or PRSUs; 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="z52559752271c453ba9f59a49aed78045">
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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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally as of March 31, 2021, we had warrants related to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_abddc1cdda9749a6b8af5dd8ac5eb3c8" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction> percent convertible senior notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>16</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-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; font-style: italic;">Adoption of ASU 2020-06</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 ASU 2020-06, which simplifies</span> the accounting for convertible debt 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. We adopted ASU 2020-06 on January 1, 2021 under the full retrospective approach, which required us to revise our prior period financial statements. This guidance impacted our accounting for outstanding convertible debt. As of March 31, 2021, we had </span><ix:nonFraction name="ions:DebtInstrumentNumberOfConvertibleNotes" id="Fact_feca9c31aa8246a4bebd7d1ae9c28967" contextRef="c20210331" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> outstanding convertible notes, our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_56766914524d4db8befa85f49ad618be" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> senior convertible notes, or </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6df698f4de8b432ebbeb7cd454cebc09" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes, which mature in December 2024, and our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ca5c77156f6644b0a75c3b7dd2769a1b" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> senior convertible notes, or </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_90499cc2339b43db9ba672cad9902593" contextRef="c20210331_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, which mature in November 2021.</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 updated guidance eliminates the cash conversion accounting model we previously followed in Accounting Standard Codification, or ASC, 470-20, which required us to separate each of our convertible debt instruments at issuance into two units of accounting, a liability component, based on our nonconvertible debt borrowing rate at issuance, and an equity component. Under ASU 2020-06, we now account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. Since we adopted ASU 2020-06 using the full retrospective approach, we were required to apply the guidance to all convertible debt instruments we had outstanding as of January 1, 2019. We recomputed the basis of each convertible debt instrument as if we accounted for each as a single unit of accounting at issuance. This update included recalculating the amortization of debt issuance costs using an updated effective interest rate. As a result of adopting ASU 2020-06, we recorded a cumulative adjustment to decrease our additional paid in capital and our accumulated deficit at January 1, 2019. We have updated these financial statements to reflect the cumulative adjustment for the periods presented. We have labeled our prior period financial statements &#8220;as revised&#8221; to indicate the change required under the new accounting guidance. Below is a summary of the change in our balance sheet at December 31, 2020 and statement of operations from our first quarter 2020 under the ASC 470-20 legacy guidance compared to the new ASU 2020-06 guidance we adopted:</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 adjustments we made to the condensed consolidated balance sheet we originally reported at December 31, 2020 to adopt ASU 2020-06 (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="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>
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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 valign="bottom" style="vertical-align: top; width: 64%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></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;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under ASU 2020-06, our revised ending balances for our 1% Notes and 0.125% Notes as of December 31, 2020 represent the principal balance of each convertible debt instrument less debt issuance costs. Additionally, because we have deferred tax assets related to our convertible debt instruments, we also adjusted these amounts as part of our adoption of ASU 2020-06. However, because we have a full valuation allowance on our deferred tax assets, there was <ix:nonFraction name="us-gaap:DeferredIncomeTaxAssetsNet" id="Fact_7bc51642648e4faea1beb838bbfe5b86" contextRef="c20201231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate202006Member_RestatementAxis_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember" unitRef="U002" decimals="-3" scale="3" format="ixt-sec:numwordsen">no</ix:nonFraction> impact to our condensed consolidated balance sheet related to 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;">The following table summarizes the adjustments we made to the condensed consolidated statement of operations we originally reported at March 31, 2020 to adopt ASU 2020-06 (in thousands):</div>
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<table cellpadding="0" cellspacing="0" id="zc88c3f1e063e47dc85bc6ded89479623" 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; 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>
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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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    <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;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></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;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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>
    <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;">$</div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">$</div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic and diluted net loss per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_6e4834a9d63845f6990514d6cfe4fd17" contextRef="c20200101to20200331_RestatementAxis_ScenarioPreviouslyReportedMember" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_6ea4ccf5074649f2976f89a0e5530985" contextRef="c20200101to20200331_RestatementAxis_ScenarioPreviouslyReportedMember" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.35</ix:nonFraction></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%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under ASU 2020-06, our revised interest expense is lower as we are no longer recording non-cash interest expense related to a debt discount. This decrease was partially offset by the increase in interest expense related to the amortization of debt issuance costs because we no longer allocate a portion of our debt issuance costs to stockholders&#8217; equity at issuance. Instead, the entire debt issuance costs were recorded as a contra-liability on our condensed consolidated balance sheet at issuance and we are amortizing them over the contractual term using an updated effective interest rate. Our updated effective interest rates for our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_75e35b87dc90426cac3e1c34a422a276" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_84a6218ff6e54d3b8f561b2b2ebbd72f" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes were <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_7633d12dfa8442d8a4437aeea1756c96" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">1.4</ix:nonFraction> percent and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_92c0796756f644e590bfc328a74e9974" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.5</ix:nonFraction> percent, respectively.</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 summarize the adjustments we made to our condensed consolidated statements of stockholders&#8217; equity we originally reported at December 31, 2020 and 2019 to adopt ASU 2020-06 (in thousands):</div>
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    <td valign="bottom" style="vertical-align: top; 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="10" 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;">December 31, 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;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</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 valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"><div style="text-align: justify; 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%; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_51b827bfd6a24b7fb340403eea1ebaca" contextRef="c20201231_RestatementAxis_ScenarioPreviouslyReportedMember_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,113,646</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td valign="bottom" style="vertical-align: top; width: 64%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></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;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" valign="bottom" style="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;">$</div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders' equity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">$</div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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<table cellpadding="0" cellspacing="0" id="z645e923d13f9452783b88b08a82563ef" 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: 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="10" 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;">December 31, 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: top; padding-bottom: 2px;">&#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;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_4a69b58d899e4f118cb2ff2dac437f57" contextRef="c20191231_AdjustmentsForNewAccountingPronouncementsAxis_AccountingStandardsUpdate202006Member_RestatementAxis_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">107,089</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:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_f21fab6a2db9499b823f91725ea0548a" contextRef="c20191231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,577,458</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; 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_f0716a76728945aeacfc77c73b2d1ec7" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes in December 2019, 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 condensed 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: left; text-indent: 36pt; 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;">In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment. Previously, we had operated as <ix:nonFraction name="us-gaap:NumberOfOperatingSegments" id="Fact_56f94f7bab79457e9475cbf5fff3ef54" contextRef="c20210101to20210331" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> operating segments, Ionis Core and Akcea Therapeutics. In October 2020, we acquired the remaining common stock of Akcea that we did not own and fully integrated Akcea&#8217;s operations into ours as of January 1, 2021.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based Compensation Expense</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, 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 condensed 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. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions. During the three months ended&#xA0;March 31, 2021 and 2020, we did <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" id="Fact_2bd665dac4244698a5e31662066fae82" contextRef="c20200101to20200331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" id="Fact_74bd6878f07a4c67acaf5d462de96fe1" contextRef="c20200101to20200331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod" id="Fact_237d17d1015343ea9cccf3349cae4ffb" contextRef="c20210101to20210331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" id="Fact_7661f202eb5e41cd85c66b4f96d91bb1" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction>t grant any stock options or RSUs to our Board of Directors. For the three months ended&#xA0;March 31, 2021 and 2020, we used the following weighted-average assumptions in our Black-Scholes calculations:</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;">Employee Stock Options:</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; font-style: italic;">ESPP:</div>
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  <tr>
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    <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;">Volatility</div></td>
    <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;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</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;">RSU&#8217;s:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_27893998ace24d7cb0e5fa8a728fcf92" contextRef="c20210101to20210331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_0b9e4755a19545e988f3c011792dba0c" contextRef="c20210101to20210331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MaximumMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. RSUs granted after June 2020 to our board of directors fully vest after <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_6ad8053af26d4d419b4294b9cd273b8f" contextRef="c20210101to20210331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MinimumMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric>. The weighted-average grant date fair value of RSUs granted to employees for the three months ended&#xA0;March 31, 2021 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_7654fd0b1d374d55b0c76914d3cd1ad7" contextRef="c20210101to20210331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">62.02</ix:nonFraction> 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;">PRSU&#8217;s:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added performance-based restricted stock units, or PRSU, awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Under the terms of the grants, <span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"><span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"><span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd">one third</span></span></span> of the PRSUs may vest at the end of <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" id="Fact_22182278d2c74c399b1aa1ec24dcb90a" contextRef="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ChiefExecutiveOfficerMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> separate performance periods spread over the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_eaaa26558fcd4695b1458629faf19186" contextRef="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ChiefExecutiveOfficerMember" format="ixt-sec:durwordsen">three years</ix:nonNumeric> following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="Fact_a18106d46f494438a0e064c9f9a96fbd" contextRef="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ChiefExecutiveOfficerMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_2200a3292de944e78e0d6c8d840bacb1" contextRef="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ChiefExecutiveOfficerMember_RangeAxis_MinimumMember" unitRef="U003" decimals="INF" scale="-2" format="ixt-sec:numwordsen">zero </ix:nonFraction>percentto <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_ce7480294faa46eab25c9b702916942c" contextRef="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ChiefExecutiveOfficerMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">150</ix:nonFraction> percent of the target number depending on our relative TSR.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of Dr. Monia&#8217;s PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to Dr. Monia for the three months ended March 31, 2021 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_f686380f406d44659451af43ea4a98c6" contextRef="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ChiefExecutiveOfficerMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">77.17</ix:nonFraction> per share.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>19</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 stock-based compensation expense for the three months ended&#xA0;March 31, 2021 and 2020 (in thousands).</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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    <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; 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;"> 2021</div></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 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>
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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>
  </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;">Selling, general and administrative 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:AllocatedShareBasedCompensationExpense" id="Fact_10a81038cb0946ad979fbbbc68e8f89e" contextRef="c20210101to20210331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,780</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;">&#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:AllocatedShareBasedCompensationExpense" id="Fact_763195b2b34c488bb094472395ab650d" contextRef="c20200101to20200331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,997</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:AllocatedShareBasedCompensationExpense" id="Fact_86792c009d4e41b3a08f1d4f8e56e11b" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">37,861</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:AllocatedShareBasedCompensationExpense" id="Fact_dff8aaed89804850bc5c9157ed3f5de6" contextRef="c20200101to20200331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">40,790</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: 12pt;"><br /></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2021, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" id="Fact_6ffe2ab146ea4bd888ad8a1bb3fc3738" contextRef="c20210331_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">101.8</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_221a3013ba19446cad9c335f9391fa1a" contextRef="c20210331_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">109.6</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_1a5a87c9d0c04b5799a90b3d2965c63f" contextRef="c20210331_AwardTypeAxis_PerformanceSharesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">3.8</ix:nonFraction> million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized non-cash stock-based compensation expense for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_86534baf9dc74c87a3bc567263180595" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">1.4</ix:nonNumeric> years, <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_94356ff2a4564b669110ba6365630dc9" contextRef="c20210101to20210331_AwardTypeAxis_RestrictedStockUnitsRSUMember" format="ixt-sec:duryear">1.8</ix:nonNumeric> years and <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_715166969b8f40d5bb56857e5eca4ce6" contextRef="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:duryear">1.7</ix:nonNumeric> years, respectively.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impact of Recently Issued Accounting Standards</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As disclosed in the &#8220;Convertible Debt&#8221; policy above within this footnote, we adopted the simplified accounting for convertible debt instrument guidance (ASU 2020-06) on January 1, 2021. Refer to the section above for the impact of adoption. We do not expect any other recently issued accounting standards to have a material impact to our financial results.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3.&#160; 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 March 31, 2021:</div>
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<div><br /></div>
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<table cellpadding="0" cellspacing="0" id="z7c460e53f6064325b6b396c3042dae44" 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; 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_26a36804df4340729bec0b2f463acda4" contextRef="c20210331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">67</ix:nonFraction></div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%;"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_3bd993e525784a5398b297b7856fe228" contextRef="c20210101to20210331" format="ixt-sec:durwordsen">one year</ix:nonNumeric> but within <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3" contextRef="c20210101to20210331" format="ixt-sec:durwordsen">two years</ix:nonNumeric></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="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="Fact_b3c2ee50dd694d208197df43360458a9" contextRef="c20210331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">20</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%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_812c571149d64b329fe4410606d76c7a" contextRef="c20210101to20210331" format="ixt-sec:durwordsen">two years</ix:nonNumeric> but within <span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797">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_8cd01e7f5688446294ec6f1b2d7e38df" contextRef="c20210331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">13</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px;"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; 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;">&#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="ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="Fact_6217a171f5784696968b178278e97ffa" contextRef="c20210331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction></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="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at March 31, 2021, <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_7de0397396204971870c9dfa3dc16f94" contextRef="c20210331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">87</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_34c87d75876e42c988ffebc06f56b6a3" contextRef="c20210101to20210331" 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We invest in available-for-sale securities</span> with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp; Poor&#8217;s, or S&amp;P, Moody&#8217;s or Fitch, respectively.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2021, we had an ownership interest of less than 20 percent in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b7edbc55e46842cb916a4ced56279788" contextRef="c20210331" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction> private companies and <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8144a98eb4174391a5f3065f3f804da4" contextRef="c20210331" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> public companies with which we conduct business. The privately held companies are 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 Antisense Therapeutics Ltd. and ProQR Therapeutics N.V.</div>
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<div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>20</span></div>
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</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>
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<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
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<table cellpadding="0" cellspacing="0" id="z6693b4efc48c4fdaaacf5939c037f0c0" 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; text-indent: -9pt; margin-left: 9pt; 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;">&#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>
    <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;">Gross Unrealized</div></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>
    <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="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>
    <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;"><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: 52%;"><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%;">&#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%;">&#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: 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_17f5c15fd8fe452b890ee866cfaa6b85" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">234,164</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_45e8bcb24cc241f2bf8f293a9b67a6a6" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">126</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_36dcce36e9b446bcb8f2877352fd5851" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" 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: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_cf007fb70961423eb9a3dd191872008b" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">234,290</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><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%;">&#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:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_7c05793868aa4afb94fcfb88fcffcb2b" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">121,776</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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_6c641805a540462f9d84d76f2727c1e9" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">220</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: 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_119b425fc08349cfbe3d5f2787dfca82" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,137</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;">&#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_60331df909a04d32a24d6b9d5d17cd03" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" 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>
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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 solid 2px; background-color: #CCEEFF;">&#160;</td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;"><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;">&#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;"><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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_401ef7ec0ee84b33b734c6646f73945d" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">890,965</ix:nonFraction></div></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;">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_e739ce406a594fdab205b3f709378b35" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">325,335</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_1465e0f748cd4bfaa10d9f2bc25757c3" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,108</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_28d6823308c14eabb012545df1bbf47e" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">245</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_dff0a77ea162428eac31903b7ae1af1c" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">328,198</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%;"><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%;">&#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:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_4069992e62e44ec39ab5806e1ac879fa" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">96,698</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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_13b8b3118986468c94cef784db3d7d85" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">36</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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_8c034ba7ebd94e519637bf63e04e1b9f" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">164</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>
    <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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_907c5df34a09413bb109221fad1ea266" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">96,570</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: 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_e43e28c5271b42a889a3b5a4967cc28d" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">59,030</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_4a47ab58cf674aa491198b0931ea7362" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">326</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_54bac431fed2433b9abbb4c98f4e8737" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">35</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_df46987f0ff442a68229243874a3a796" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">59,321</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%;"><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%;">&#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:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_9945c8a3aa274e52aa7dfeabc6567ab4" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,515</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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_2aa6d352ef954e92b94b3e1d7fb0194a" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">81</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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_e6854048f6c941b08d43417760c49b8d" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">25</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>
    <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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_d4953054b98b42dba9d5bed9a4393226" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,571</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: 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</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%; 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_908bc226da6b49d3ac3ca3bfc29507b9" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</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>
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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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_07ec3f05fd0e447092c976290e113a2c" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,213</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;"><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;">&#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:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_2b2ee63d727e423482b317c18a37ce81" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">521,811</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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_22456af2bd1a42a5aaa84149b3a6373e" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,551</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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_3f93907b739e4f8a80f71070bbbc98e2" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">489</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_33930b14001f46ccb9bf26b44f06a253" contextRef="c20210331_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">524,873</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: 52%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td 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_c63efe923e13426992c34154ca0ceb66" contextRef="c20210331_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,410,407</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_4d9475d7048b443985ccf0e54c482dde" contextRef="c20210331_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,027</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_abe680e773e045d898d7e780327a8001" contextRef="c20210331_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">596</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_ed64a9779a3842959199d38607dc68f6" contextRef="c20210331_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,415,838</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%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</span></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%;">&#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>
    <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: 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_795298199a7149089987fd608d910788" contextRef="c20210331_InvestmentTypeAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedGain" id="Fact_95a1e63d6d4c49f48092f55cc7344a6f" contextRef="c20210101to20210331_InvestmentTypeAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_720e14f204184668ac412128829c1d4c" contextRef="c20210101to20210331_InvestmentTypeAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,514</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_c9668cdfca24444facba84f5586a8b21" contextRef="c20210331_InvestmentTypeAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,198</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;"><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;">&#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:EquitySecuritiesFvNiCost" id="Fact_642c9681829a411280b706605512aec4" contextRef="c20210331_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,062</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:EquitySecuritiesFvNiUnrealizedGain" id="Fact_5465f26f407f4c8cbf1a7f4bc78d58bb" contextRef="c20210101to20210331_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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; 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:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_8f26e7f4482346919fb9fd971a0e1bd2" contextRef="c20210101to20210331_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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_c86ece7c238c409db75f4e86d57eaa03" contextRef="c20210331_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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; 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>
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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 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:EquitySecuritiesFvNi" id="Fact_10dc545d20404abda7146b5a706c0e00" contextRef="c20210331_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,198</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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    <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>
    <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="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_29d056dd0bc546a5b95f13a73db1588f" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,450,036</ix:nonFraction></div></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;">&#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="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>
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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; 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_b358568c049541b1856e64106205b629" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">514,182</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="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_e219351c2ba44027b99a7eb94f4fb4bd" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">41</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_baf860337cb14231b2612b277c5a61c8" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">516,335</ix:nonFraction></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%;">&#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="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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2130cf6d51914dc0afd1eccb0e4dfdad" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">94,586</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: 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>
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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: 52%;"><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%; 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="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%; 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_a7ab9739b25b4394ab74500c2a29c823" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_41c6c9ee3b0e47fb92892c59f6b90756" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_706d28fef2024eca9d1840a75a6914ff" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_e8fe0e2b39a24133b8d962321697a512" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" 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;"><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;">&#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:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_5d62eb1de663460d8a9d559d81878a58" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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; 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_32d0c20dd09a4965be6545f5ef1e1d0e" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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; 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_a65f661f76de418c8ded0d80f7684b50" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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; 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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_5269f1e3ba9b4b5f9397e201edccca32" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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; 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_a2fd30f9900b415194cd94d357af784b" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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_34ab02ad304f441abe8a81962651c7ce" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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_3d4b4abb3a29485786b07cbc63b828cb" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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_e00dab3b4cb04062a2e6a17f853d0e52" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">329,980</ix:nonFraction></div></td>
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  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><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%;">&#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:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_d714f0d4eecc4d92b9b830449bba7fd1" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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%; 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_270ced43418a4c2faa9a7f0a3bd756eb" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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%; 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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  </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>
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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>
    <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: 52%;"><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%;">&#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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_31520233cfb642e0bb7685bb15133f3a" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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%; 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>
    <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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_e281a6848521414491c86fcd9f85c8a9" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">31,854</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: 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_8039b5caa1e74523933ab777edc0cc55" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_ce80a712118d48bca2b5173f22d877be" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_7f14ae8a216045b6b0f1cba03a06d496" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_5191d04da6c34987a3faa2edb62ca0eb" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" 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;"><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;">&#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:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_d8f9bd55d10c46e8a7923b828bf66f7b" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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; 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_9edb30f88d124e4f98e5fc6733baa317" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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; 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_35b1772ea2884933bfa48eab5441097a" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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; 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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_bd78e79378ff4eecb24ada86ee7d4685" contextRef="c20201231_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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; 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: 27pt; 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_d8842e093daf4aa8a441e191da86ea99" contextRef="c20201231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_4a16a27e0c4144fea9d33948c111d40b" contextRef="c20201231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">8,577</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_5d60bf6074c241728013af9aebe4f553" contextRef="c20201231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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_282a1da5440143508a579978a45d2601" contextRef="c20201231_InvestmentTypeAxis_DebtSecuritiesMember" unitRef="U002" 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>
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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>
    <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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    <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;">$</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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>
    <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_8651c4c7cf0b40ec9603b79cfd50d43b" contextRef="c20201231_InvestmentTypeAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,031</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: 52%; padding-bottom: 2px;"><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;">&#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:EquitySecuritiesFvNiCost" id="Fact_2faff3973c0f4ab0bd4fcffd3307bce8" contextRef="c20201231_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,062</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:EquitySecuritiesFvNiUnrealizedGain" id="Fact_e3dee8ea479d4e8fbda5e68ba7814a7e" contextRef="c20200101to20201231_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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; 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:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_53a829bbd230481e83c9e355f575a8b7" contextRef="c20200101to20201231_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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_90b3f028c4c64df180eb902de39038aa" contextRef="c20201231_InvestmentTypeAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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; 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;">&#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:EquitySecuritiesFvNiCost" id="Fact_cfbea931b88e4baf9112a7e54d02cbfc" contextRef="c20201231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U002" 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;">&#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:EquitySecuritiesFvNiUnrealizedGain" id="Fact_5e7e8a83411f4b40bf00d16a3e60d487" contextRef="c20200101to20201231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U002" 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;">&#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:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_d45ad7a12cac403ea2d5a2edb37a0eed" contextRef="c20200101to20201231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U002" 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;">&#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:EquitySecuritiesFvNi" id="Fact_8bd47c89fd1645cfa78adda562a9364e" contextRef="c20201231_InvestmentTypeAxis_EquitySecuritiesMember" unitRef="U002" 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;"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</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="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_6808aa03681547cca1d6c98d32aab031" contextRef="c20201231" unitRef="U002" 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; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_f7a5c21d883b40c784a842b4eab86b9d" contextRef="c20201231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,515</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_bf106be9d5824af3aa9e4c635557fb8a" contextRef="c20201231" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_ecad1868d9ae4c4cb68ebd3c78a85d30" contextRef="c20201231" unitRef="U002" 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; white-space: nowrap;">&#160;</td>
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<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_9e6646755dcd4486a84d8d59413154b920" continuedAt="Text_9e6646755dcd4486a84d8d59413154b921"><ix:continuation id="Text_ca9ac8e921c74fa4a7de49e5c279b2cb6" continuedAt="Text_ca9ac8e921c74fa4a7de49e5c279b2cb7">
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  <tr>
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    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_305e1d6b0b66460686148b2ce6e01d9b" 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>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_9e6646755dcd4486a84d8d59413154b921" continuedAt="Text_9e6646755dcd4486a84d8d59413154b922"><ix:continuation id="Text_ca9ac8e921c74fa4a7de49e5c279b2cb7" continuedAt="Text_ca9ac8e921c74fa4a7de49e5c279b2cb8">
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</ix:continuation></ix:continuation><ix:continuation id="Text_9e6646755dcd4486a84d8d59413154b922" continuedAt="Text_9e6646755dcd4486a84d8d59413154b923"><ix:continuation id="Text_ca9ac8e921c74fa4a7de49e5c279b2cb8" continuedAt="Text_ca9ac8e921c74fa4a7de49e5c279b2cb9">
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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>
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  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_9e6646755dcd4486a84d8d59413154b923" continuedAt="Text_9e6646755dcd4486a84d8d59413154b924"><ix:continuation id="Text_ca9ac8e921c74fa4a7de49e5c279b2cb9" continuedAt="Text_ca9ac8e921c74fa4a7de49e5c279b2cb10">
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</ix:continuation></ix:continuation><ix:continuation id="Text_9e6646755dcd4486a84d8d59413154b924" continuedAt="Text_9e6646755dcd4486a84d8d59413154b925"><ix:continuation id="Text_ca9ac8e921c74fa4a7de49e5c279b2cb10" continuedAt="Text_ca9ac8e921c74fa4a7de49e5c279b2cb11">
<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="z860f6d5bdfcf49cf808f1c8cbb8e1031">
  <tr>
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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;"><ix:footnote id="Foot_20cf8a92586d4d88bc45b040cb662025" 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: 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_55aad856d839435daad2d772a2ea1bc5" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_c2358dd198c64701830a1c465d38fa731">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_c2358dd198c64701830a1c465d38fa731" continuedAt="Foot_c2358dd198c64701830a1c465d38fa732"> 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_c2358dd198c64701830a1c465d38fa732">.</ix:continuation></span></div></td>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our investments we consider to be temporarily impaired at </span>March 31, 2021<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. 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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    <td valign="bottom" style="vertical-align: bottom; 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;">Debt securities issued by the U.S. Treasury</div></td>
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  <tr>
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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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    <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;">&#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="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:AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_2e5fc3a4028e4761b5d0ae37c8a00f62" contextRef="c20210331_InvestmentTypeAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">27</ix:nonFraction></div></td>
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  </tr>
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    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;">&#160;</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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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4.&#160; 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: justify; text-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 present the major security types we held at </span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that we regularly measure and carry at fair value. As of </span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>we did <ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_5452870d9e974db08d39afd2a8ea9a29" contextRef="c20201231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_a73435ac252543159195ea45d7f0d744" contextRef="c20210331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any investments that we valued using Level 3 inputs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. 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):</span></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;">At</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2021</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; 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>
    <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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_ab8b93d31763462f825afbb8d94ca1c5" contextRef="c20210331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">372,050</ix:nonFraction></div></td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
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    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div></td>
    <td 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:AvailableForSaleSecurities" id="Fact_1b769ef466ea447fba9ad51918866940" contextRef="c20210331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">776,776</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:AvailableForSaleSecurities" id="Fact_1a622d10285342d4ab574fbc330e9b6a" contextRef="c20210331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</div></td>
    <td 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:AvailableForSaleSecurities" id="Fact_4ce9866198094ab9bb0fba527e9f7a46" contextRef="c20210331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">177,563</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; 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>
    <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:AvailableForSaleSecurities" id="Fact_2e48b747b93e49a19ff9c8c29a110e0c" contextRef="c20210331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (3)</div></td>
    <td 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:AvailableForSaleSecurities" id="Fact_c11eb07ea3324e24902d31be146e2aba" contextRef="c20210331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">156,545</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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  <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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  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (4)</div></div></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:EquitySecuritiesFvNi" id="Fact_eaa3b06235c44c048a5d428f0fd68f15" contextRef="c20210331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,198</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:EquitySecuritiesFvNi" id="Fact_816cd8cab6a1437db6b65fcb66362f2b" contextRef="c20210331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></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%; 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;">&#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: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>22</span></div>
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<table cellpadding="0" cellspacing="0" id="z8fa75e640870498fb69868b78d69ca2a" 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: 8pt;"></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>
    <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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  <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; 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:CashAndCashEquivalentsFairValueDisclosure" id="Fact_cf31ecc6404147a58c29e5014d56f016" contextRef="c20201231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">221,125</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="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>
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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%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_f7afdd3696234671b44470fdeb5cc1ab" contextRef="c20201231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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:AvailableForSaleSecurities" id="Fact_1da099e8f70b413ba14d2cc70facff8a" contextRef="c20201231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">846,315</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: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</div></td>
    <td colspan="1" 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:AvailableForSaleSecurities" id="Fact_785896601b0b484f948508e26185bbc6" contextRef="c20201231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">174,861</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>
    <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:AvailableForSaleSecurities" id="Fact_f940b884e12a40fb87b29e49ae479b99" contextRef="c20201231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</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="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>
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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%;">&#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>
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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:EquitySecuritiesFvNi" id="Fact_d4c5e9d825a04573948d40fecaafe4a3" contextRef="c20201231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,031</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>
    <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:EquitySecuritiesFvNi" id="Fact_cb78c50644f34cb6b9de0f25ce8bab73" contextRef="c20201231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" 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>
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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>
    <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>
    <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:AssetsFairValueDisclosure" id="Fact_568137f2518f467bb9256c293c42f530" contextRef="c20201231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,163,710</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><br /></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines on our condensed consolidated balance sheet:</div>
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<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_3fd7eed8c1cc4032b74aa771ebfdad3812" continuedAt="Text_3fd7eed8c1cc4032b74aa771ebfdad3813"><ix:continuation id="Text_cd7be74ad66e43fa8e3fa8c541992c858" continuedAt="Text_cd7be74ad66e43fa8e3fa8c541992c859">
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</ix:continuation></ix:continuation><ix:continuation id="Text_3fd7eed8c1cc4032b74aa771ebfdad3813" continuedAt="Text_3fd7eed8c1cc4032b74aa771ebfdad3814"><ix:continuation id="Text_cd7be74ad66e43fa8e3fa8c541992c859" continuedAt="Text_cd7be74ad66e43fa8e3fa8c541992c8510">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_3fd7eed8c1cc4032b74aa771ebfdad3814" continuedAt="Text_3fd7eed8c1cc4032b74aa771ebfdad3815"><ix:continuation id="Text_cd7be74ad66e43fa8e3fa8c541992c8510" continuedAt="Text_cd7be74ad66e43fa8e3fa8c541992c8511">
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</ix:continuation></ix:continuation><ix:continuation id="Text_3fd7eed8c1cc4032b74aa771ebfdad3815" continuedAt="Text_3fd7eed8c1cc4032b74aa771ebfdad3816"><ix:continuation id="Text_cd7be74ad66e43fa8e3fa8c541992c8511" continuedAt="Text_cd7be74ad66e43fa8e3fa8c541992c8512">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_3fd7eed8c1cc4032b74aa771ebfdad3816" continuedAt="Text_3fd7eed8c1cc4032b74aa771ebfdad3817"><ix:continuation id="Text_cd7be74ad66e43fa8e3fa8c541992c8512" continuedAt="Text_cd7be74ad66e43fa8e3fa8c541992c8513">
<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="z6f9607f6620b4bbd9672800078d88f17">
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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>
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<div><br /></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="z77f49d1f8884459da3bd041fd3da0886">
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    <td style="width: 18pt; 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_67f6ff09f4d443248a7bd7fe03ce1bd9" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in other current assets on our condensed consolidated balance sheet.</ix:footnote></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;">(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_f0cb78a83b31476988ccfd169edddb78" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US" continuedAt="Foot_8f5e944cdb1d47c38e3df16c23e8d8071">$<ix:nonFraction name="us-gaap:AvailableForSaleSecurities" id="Fact_e1137a0d228f4c288dbe6225420e82af" contextRef="c20201231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">17.5</ix:nonFraction></ix:footnote><ix:continuation id="Foot_8f5e944cdb1d47c38e3df16c23e8d8071"> million included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</ix:continuation></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;">Convertible Notes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9f5be1954e89462eb0b4b557e590a667" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dfc304a4577d4a8b8ccf97e7be8f9791" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes had a fair value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_08dde5b870bf48ad8f56230371fe5c23" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">314.6</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_886896b6a5b643a387fb328dcc366ca9" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">527.3</ix:nonFraction> million at March 31, 2021, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Collaborative Arrangements and Licensing Agreements</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;">Below, we have included our Biogen collaboration, which is our only collaboration with substantive changes during </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2021</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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; font-weight: bold;">Biogen</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 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_92d0ca6977364d5fb2c03318547a94af" contextRef="c20210331_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 March 31, 2021, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_4de0101278b94f98a15dfb2c4990f91e" contextRef="c20210331_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-8" scale="9" format="ixt:numdotdecimal">2.9</ix:nonFraction> billion from our Biogen collaborations.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>23</span></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>
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<table cellpadding="0" cellspacing="0" id="z4f1f3cff556a4eeead54494912e5f024" 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="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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31,</div></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;">2021</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;">2020</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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    <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>
    <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>
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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>
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    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</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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    <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>
</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our condensed consolidated balance sheet at March 31, 2021 and December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>included deferred revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_5178e097d0c342cf84072f17ad124e39" contextRef="c20210331_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">447.7</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_7b83a105f51e48c19c4fa834b14d4660" contextRef="c20201231_TypeOfArrangementAxis_CollaborativeArrangementsAndLicensingAgreementsBiogenMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">465.8</ix:nonFraction> million, respectively, related to our relationship with Biogen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the first three months of 2021, we did not have any changes to our performance obligations, transaction price or the timing in which we expect to recognize revenue under our Biogen collaborations.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we achieved a $<ix:nonFraction name="ions:MilestonePaymentAchieved" id="Fact_ab91654b7168476fa5495fb1d76b719d" contextRef="c20210401to20210430_ProductOrServiceAxis_Ion541Member_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment from Biogen when Biogen advanced ION541, an investigational medicine targeting ataxin 2 to treat patients with ALS. We will achieve the next payment of $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_11c23dc721af4581b81256e8aebe8b08" contextRef="c20210430_StatementScenarioAxis_ScenarioPlanMember_TypeOfArrangementAxis_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">8</ix:nonFraction> million if Biogen advances one of the medicines under our 2013 strategic neurology collaboration.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. 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; font-style: italic;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6084a279781c4f6f9d255000ab9021c3" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction> Percent</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Convertible Senior Notes and Call Spread</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 April 2021, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_31b7ba9c70ea47c98e3db30445a91628" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">632.5</ix:nonFraction> million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6552a8e4040f43878523b992f32fce9e" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction> percent convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9dafbe4ac36f4acab7c5417e2b16fdb9" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes, to repurchase $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_367cca58a7ca4ff88703902e4e0bd9d7" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">247.9</ix:nonFraction> million in principal of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_daaf05b5284740438b6e8f119ed98382" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes for $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_b88be17da074442d8e0174eda1c066ff" contextRef="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">257.0</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;">Following the closing of the debt transaction in April 2021, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_851b6e16263b47a8a5a3b794b32dee59" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>%</span> Notes outstanding (amounts in millions except interest rate and price per share data):</div>
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<table cellpadding="0" cellspacing="0" id="z88e151c0fc7e49d29682b6fa6b7ce8ae" 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c94bff2160504f00b4aff81b982396f8" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>%</span> Notes</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: 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;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_edd5ff3b856642199ff86499cf0281a8" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">632.5</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>
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    <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;"><span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde">April 2026</span></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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dce4bbae7b2a40908908ca4da1034984" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</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>
  </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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_b923c911082f4a9dbe578941ab6ba57e" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">57.84</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_b9aacb5cbdd246a29518869cf1580bba" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">76.39</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: top; width: 88%;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td 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="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_36af5452ef2d4158ba6f36e437b52979" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">10.9</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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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a1c65db2db5e45bf9144abb23a3708cd" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes by increasing the effective conversion price on our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_47594a78eeb74261b797d8f322986fa4" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes. We increased our effective conversion price to $<ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_adfab887b13140eda35dd28df11ca681" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">76.39</ix:nonFraction> with the same number of underlying shares as our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1e893f3eccd04fa886b5729d9095bb3a" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes. The call spread cost us $<ix:nonFraction name="ions:CallSpread" id="Fact_9cea2f5d760e42c0a7580446a66d3538" contextRef="c20210401to20210430_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">46.9</ix:nonFraction> million, of which $<ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_36a469c4005348aa8141ff489585a08c" contextRef="c20210401to20210430_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">136.7</ix:nonFraction> million was for the note hedge purchase, offset by $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfWarrants" id="Fact_9dc32db714544a28860e525c4fab30e8" contextRef="c20210401to20210430_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">89.8</ix:nonFraction> million we received for selling the warrants. Similar to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_327d187d871445adb18503b7c83d8bb1" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1bb651c30fc64b0db83da188f8aae2f8" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes. The note hedges will expire upon maturity of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ca5f6c96b1124b2989fd762efdf51a1e" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_01da5b0bd9a8481f8816fdd4ee0aa0c5" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes. The holders of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7c0a89b92f644ec1a10cc74660014eab" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes do not have any rights with respect to the note hedges and warrants.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_76ff515a60454ce18e1a9984840953ae" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction> Percent Convertible Senior Notes and Call Spread</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2021, we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e999f0a79cc5454dbb35d79507c6bf14" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):</div>
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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: top;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec">December 2024</span></div></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; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</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>
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  <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>
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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%; 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:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_257883a038234987a42360f37188d9b5" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">123.38</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: 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%;">&#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>
    <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;">Unamortized 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;"><ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_4c74194ec2b048479ab4aa398e01add7" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">8.1</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>
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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;">In conjunction with the issuance of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fce48022202d43bb90824a8ab622ba1e" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes in December 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_74c63dcb37a94b7c96fcda23934eccde" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes by increasing the effective conversion price on our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5e16fd8ed7c44c38864b21191b33ad87" contextRef="c20210331_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;">. We increased our effective conversion price to $</span><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_706c33f17c1047e2b303834e2dfa9903" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" 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><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8ada2275fc3149ba9239349b360d3ff0" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes. The call spread cost us $</span><ix:nonFraction name="ions:CallSpread" id="Fact_376edf8306554bc9be15b3e5059f9689" contextRef="c20191201to20191231" unitRef="U002" 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_63109fd55a644feaa1ceeef8ebde9e37" contextRef="c20191201to20191231" unitRef="U002" 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_821561db37bf489ea047c585d83d7fb2" contextRef="c20191201to20191231" unitRef="U002" 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. Similar to our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8508261275f046e4bd44878636855c30" contextRef="c20210331_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;">, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a599520206b24338ba155a460138e93b" contextRef="c20210331_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;">. The note hedges will expire upon maturity of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9d674b898cb1469d9b4c18232244d3d9" contextRef="c20210331_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;">, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dcf07dd5cb7a40b58bbb604e293f91c3" contextRef="c20210331_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;">. The holders of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_cf200a768fcb4dcb9dda4aaad67a8130" contextRef="c20210331_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;"> do not have any rights with respect to the note hedges and warrants.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount paid for the note hedges and the amount received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fd23717a1d4d4ec2ae3decc69589c581" contextRef="c20210331_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;">At March 31, 2021, we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e4f1e352ad994f57a4cc8c35adf0de01" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):</div>
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<table cellpadding="0" cellspacing="0" id="z18f2e28c3bf848fab4205a897b0abb11" 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;">&#160;</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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_93e7bc22df754f868a273355f581746b" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes</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: 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;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_5a86d447cb1d43a681361fcd232fdf9e" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">309.9</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>
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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;">&#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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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we repurchased $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_5733913e61d243aba64ac5cdde17967a" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">247.9</ix:nonFraction> million in aggregate principal amount of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7dce99cb33884aa695f60d9714cdbc63" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes in privately negotiated transactions. As a result, in April 2021, the remaining principal outstanding for our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_99c3a77d5e074b5dac8c34c404485ae9" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes was $<ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_d34714394d614ef389f51b891031c091" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">62.0</ix:nonFraction> million, resulting in <ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_6138d64ae2c24a00aa778b9e957581a8" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">0.9</ix:nonFraction> million shares of common stock subject to conversion. As a result of the repurchase, we reclassified the repurchased portion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_67b66035ddd24a458d6556cf497ca981" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes from current to non-current liabilities on our condensed consolidated balance sheet as of March 31, 2021 because we replaced this portion of our outstanding debt with long-term debt.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Other Terms of Convertible Senior Notes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b2fc1c75f5c641f2b66eff5bf9e11829" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>%, <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c98e7aaf45cf42a78ac646beebca0a17" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_081e13ee19fb4f5e954bcb24cbc4843c" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to <ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_01965def6c8647aa98fa503feb99c304" contextRef="c20210101to20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_d0a7473945cc459e81637c010df801c1" contextRef="c20210101to20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_236a491df6914133bf71b4e04a765967" contextRef="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction></ix:nonFraction></ix:nonFraction> percent of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>25</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Severance and Retention Costs</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;">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;">As a result of the Akcea Acquisition in October 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total estimated severance and retention expenses related to the Akcea Acquisition (in millions):</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>
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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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    <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;">Expenses incurred in the three months ended March 31, 2021</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 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;">Remaining estimated expenses to be recognized through October 2021</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>
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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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our severance and retention expenses related to the Akcea Acquisition that we recognized during the three months ended&#xA0;March 31, 2021 (in millions):</div>
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  <tr>
    <td valign="bottom" style="vertical-align: top; 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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    <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;">Research, development and patent expenses</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 amounts related to the Akcea Acquisition that we included in accrued compensation for the period indicated (in millions):</div>
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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%; 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: 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:RestructuringReserve" id="Fact_e807dd99b36c4f39abd08c101618de3b" contextRef="c20210331_RestructuringCostAndReserveAxis_AkceaAcquisitionMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">11.1</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="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The reserve adjustments during the period primarily related to forfeitures of severance and retention payments as a result of employee terminations before they earned the amounts.</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;">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;">As a result of restructuring our European operations, or Restructured European Operations, in December 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total severance and retention expenses related to our Restructured European Operations (in millions):</div>
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<table cellpadding="0" cellspacing="0" id="z4017ce63a44d40988c5306fc8d86c8e2" 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;">&#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: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total estimated expenses</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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  <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;">Expenses incurred in the three months ended December 31, 2020</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="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>
  </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;">Remaining estimated expenses through October 2021</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>
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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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the severance and retention expenses related to our Restructured European Operations that we recognized during the three months ended&#xA0;March 31, 2021 (in millions):</div>
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    <td valign="bottom" style="vertical-align: top; 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: top; 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;">March 31, 2021</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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    <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:RestructuringReserveNetExpense" id="Fact_8e1bd12883084ff5bc5718be28d1a948" contextRef="c20210101to20210331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember_RestructuringCostAndReserveAxis_RestructuredEuropeanOperationsMember" unitRef="U002" 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; white-space: nowrap;">&#160;</td>
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    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; 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="ions:RestructuringReserveNetExpense" id="Fact_b533a515bf5845edbb191a6138557b8c" contextRef="c20210101to20210331_RestructuringCostAndReserveAxis_RestructuredEuropeanOperationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.7</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the severance and retention reserve amounts related to our Restructured European operations that we included in accrued compensation for the periods indicated (in millions):</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: top; 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;">March 31, 2021</div></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;">Beginning balance</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:RestructuringReserve" id="Fact_f4dc356cc35e41819e53ad91d67a8344" contextRef="c20201231_RestructuringCostAndReserveAxis_RestructuredEuropeanOperationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">12.4</ix:nonFraction></div></td>
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    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: left; text-indent: 18.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts expensed during the period</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:RestructuringCharges" id="Fact_cb757748da2341e1b7a489c3e555bc70" contextRef="c20210101to20210331_RestructuringCostAndReserveAxis_RestructuredEuropeanOperationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.2</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; text-indent: 18.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Reserve adjustments during the period</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:RestructuringReserveAccrualAdjustment1" id="Fact_c929758cfc9d4485baec478ede9e8f83" contextRef="c20210101to20210331_RestructuringCostAndReserveAxis_RestructuredEuropeanOperationsMember" unitRef="U002" decimals="-5" scale="6" sign="-" format="ixt:numdotdecimal">1.5</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%;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net amount expensed during the period</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="ions:RestructuringReserveNetExpense" id="Fact_0a1d55f37139484683f834ee3593315a" contextRef="c20210101to20210331_RestructuringCostAndReserveAxis_RestructuredEuropeanOperationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.7</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;">&#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:PaymentsForRestructuring" id="Fact_53493cca53fa42ecaa142d926d48a995" contextRef="c20210101to20210331_RestructuringCostAndReserveAxis_RestructuredEuropeanOperationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">11.9</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: top; width: 88%; padding-bottom: 4px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance</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:RestructuringReserve" id="Fact_ced2500e81264495802d37cead651693" contextRef="c20210331_RestructuringCostAndReserveAxis_RestructuredEuropeanOperationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.2</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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The reserve adjustments during the period primarily related to tax expense adjustments.</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;">Restructured North American TEGSEDI 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 April 2021, we entered into a distribution agreement with Sobi for TEGSEDI in North America. Under the terms of the distribution agreement, we will retain the marketing authorizations for TEGSEDI in the U.S. and Canada. We will continue to supply commercial product to Sobi and manage regulatory and manufacturing processes, as well as relationships with key opinion leaders. We will also continue to lead the TEGSEDI global commercial strategy. Sobi will otherwise have responsibility for commercializing TEGSEDI in the U.S. and Canada and will assume these activities by August 2021.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In connection with restructuring our North American TEGSEDI operations, or Restructured North American TEGSEDI Operations, we enacted a plan to reorganize our Akcea workforce in North America to better align with the needs of our business, or the Reorganization Plan, and to focus on our wholly owned pipeline. Under the Reorganization Plan, we expect to incur restructuring charges in the range of $<ix:nonFraction name="us-gaap:RestructuringAndRelatedCostExpectedCost1" id="Fact_a1ce2380c90444f3af50169f17620fbc" contextRef="c20210331_RangeAxis_MinimumMember_RestructuringCostAndReserveAxis_RestructuredNorthAmericanTEGSEDIOperationsMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">11</ix:nonFraction> million to $<ix:nonFraction name="us-gaap:RestructuringAndRelatedCostExpectedCost1" id="Fact_d58d39a773a8475589af34185527dcac" contextRef="c20210331_RangeAxis_MaximumMember_RestructuringCostAndReserveAxis_RestructuredNorthAmericanTEGSEDIOperationsMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">14</ix:nonFraction> million principally in the second quarter of 2021.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>27</span></div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">MANAGEMENT&#8217;S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS</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;">In this Report on Form 10-Q, unless the context requires otherwise, &#8220;Ionis,&#8221; &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us,&#8221; means Ionis Pharmaceuticals, Inc. and its wholly owned affiliate, Akcea Therapeutics, Inc.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Forward-Looking Statements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">In addition to historical information contained in this Report on Form 10-Q, the Report 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. 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 COVID-19 could have on our business, and including 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 and described in additional detail in our annual report on Form 10-K for the year ended December 31, 2020, which is on file with the U.S. Securities and Exchange Commission and is available from us, and those identified within Part II Item 1A. Risk Factors of this Report. 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>
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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 address a broad range of diseases. We are primarily focused on two core franchises: neurology and cardiometabolic. 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 ongoing with five medicines: tofersen for SOD1-ALS, IONIS-TTR-L<sub style="font-family: Times;">Rx</sub> for transthyretin, or TTR, amyloidosis, IONIS-APOCIII-L<sub style="font-family: Times;">Rx</sub> for familial chylomicronemia syndrome, or FCS, pelacarsen for lipoprotein(a), or Lp(a), driven cardiovascular disease and ION363 for amyotrophic lateral sclerosis, or ALS, with mutations in the fused in sarcoma gene, or FUS.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">In April 2021, we entered into a distribution agreement with Sobi for TEGSEDI in North America. Under the terms of the distribution agreement, we retained the marketing authorizations for TEGSEDI in the U.S. and Canada. We will continue to supply commercial product to Sobi and manage regulatory and manufacturing processes, as well as relationships with key opinion leaders. We will also continue to lead the TEGSEDI global commercial strategy. In connection with the agreement, we enacted the Reorganization Plan to reorganize our Akcea workforce in North America to better align with the needs of our business and to focus on our wholly owned pipeline. Under the Reorganization Plan, we expect to incur restructuring charges in the range of $11 million to $14 million principally in the second quarter of 2021.</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 a 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 March 31, 2021, more than 11,000 patients were on SPINRAZA therapy in markets around the world. Through March 31, 2021, we have earned more than $1.4 billion in revenues from our SPINRAZA collaboration, including approximately $1 billion 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. We launched TEGSEDI in the U.S. and the European Union, or EU, in late 2018. In 2021, we began selling TEGSEDI in Europe through our distribution agreement with Sobi. Additionally, in the second quarter of 2021, Sobi also began distributing TEGSEDI in the U.S. and Canada. 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;">WAYLIVRA is a once weekly, self-administered, subcutaneous medicine that received conditional marketing authorization in May 2019 from the European Commission, or EC, as an adjunct to diet in adult patients with genetically confirmed FCS and at high risk for pancreatitis. We launched WAYLIVRA in the EU in the third quarter of 2019. In 2021, we began selling WAYLIVRA in Europe through our distribution agreement with Sobi. 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 the National Health Surveillance Agency (Ag&#234;ncia Nacional de Vigil&#226;ncia Sanit&#225;ria), or ANVISA.</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: justify; text-indent: 36pt; 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.</div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Phase 3 medicines 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;">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; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">IONIS-TTR-L<sub style="font-family: Times;">Rx</sub>: Enrollment is 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; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">IONIS-APOCIII-L<sub style="font-family: Times;">Rx</sub>: Enrollment is ongoing in the BALANCE Phase 3 study in patients with FCS</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;">Pelacarsen: Enrollment is ongoing in Novartis Pharma AG&#8217;s Lp(a)HORIZON Phase 3 cardiovascular outcome study</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;">ION363: We recently initiated a Phase 3 study in patients with FUS-ALS, the most common cause of juvenile-onset ALS</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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Financial Highlights</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 financial results (in millions):</div>
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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;">Three Months Ended March 31,</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;">2021</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;">2020</div></td>
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    <td colspan="2" valign="bottom" style="vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(as revised*)</div></td>
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    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div></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>
    <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;">111.6</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">133.4</div></td>
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    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
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    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">203.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">194.5</div></td>
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    <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;">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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(92.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(61.1</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>
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    <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;">Net 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(89.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(49.9</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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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</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 revenue for the first quarter of 2021 was $111.6 million. Our commercial revenue in the first quarter of 2021 was consistent with the same period last year. As we complete the transition of TEGSEDI operations in North America to Sobi, our commercial revenue from product sales will shift to distribution fee 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 our R&amp;D revenue from multiple sources that can fluctuate depending on the timing of events. Our R&amp;D revenue decreased in the first quarter of 2021 compared to the same period in 2020 primarily because we earned more milestone payments in the first quarter of 2020 than in the first quarter of 2021. We expect our R&amp;D revenue to increase in the second half of 2021 compared to the first half.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses for <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the first quarter of 2021</span> were $203.6 million and increased over the same period in 2020, principally due to our investments in advancing our late-stage wholly owned pipeline. In addition, we incurred approximately $7 million in costs related to the Akcea Acquisition and Restructured European Operations, primarily comprised of severance and retention 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 expect our operating expenses to continue to increase during the rest of 2021 as we continue to advance our strategic priorities. Additionally, we expect to incur an additional $11 million to $14 million of restructuring costs, principally in the second quarter of 2021, related to the Restructured North American TEGSEDI Operations to better align with the immediate needs of our business and to focus on our wholly owned pipeline. We also expect to recognize the majority of the remaining severance and retention costs related to the Akcea Acquisition and Restructured European Operations transactions in the second quarter of 2021. See Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Severance and Retention Costs</span>, for additional details.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We ended the first quarter of 2021 with $1.8 billion in cash and short-term investments. In April 2021, we issued $632.5 million of 0% senior convertible notes due in April 2026 and repurchased $247.9 million of our 1% senior convertible notes. In conjunction with these transactions, we also executed a call spread to increase the effective conversion price of the 0% senior convertible notes to $76.39. After giving effect to these transactions, our pro forma cash, cash equivalents and short-term investments was $2.1 billion. We believe our strong financial position should enable us to continue to execute on our corporate goals throughout this year and beyond, including developing and commercializing medicines within our wholly owned pipeline.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recent Business Updates</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">First Quarter 2021 Marketed Products Highlights</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;">SPINRAZA: a global foundation-of-care for the treatment of SMA patients of all ages</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;">$521 million in worldwide sales in the first quarter</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="zc2c27cb552944bcd89d1ce45db60c497">
  <tr>
    <td style="width: 54pt;"></td>
    <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;">More than 11,000 patients worldwide were on therapy at the end of the first quarter across post-marketing, expanded access and clinical trial settings</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="z52aa5dc97c054d2799757471021e8195">
  <tr>
    <td style="width: 54pt;"></td>
    <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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Higher-dose </span>SPINRAZA demonstrated safety and tolerability consistent with the currently approved dose in the open-label safety cohort of the DEVOTE study, enabling enrollment in the blinded, pivotal cohort to get underway</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="z3c29eb89d00e44d296dc514b77dcd181">
  <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;">TEGSEDI and WAYLIVRA: important medicines approved for the treatment of patients with severe rare diseases</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="z2fdb7a4b8ee24987bdf2f72a0bbc3b28">
  <tr>
    <td style="width: 54pt;"></td>
    <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;">Completed the transition of European operations to Sobi and expanded the distribution agreement to include North American TEGSEDI operations</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">First Quarter 2021 and Recent Pipeline Events</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="z8a58aa5085f04179a26679959b1cd405">
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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;">Phase 3 Pipeline: growing and positioned for 12 or more products on the market in 2026</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="zede259da1d324d579fe26286d7071fd3">
  <tr>
    <td style="width: 54pt;"></td>
    <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;">Advanced ION363 into a Phase 3 study in patients with FUS-ALS</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="z859dbde6648d4d76b9ff29b8f92dfc95">
  <tr>
    <td style="width: 54pt;"></td>
    <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;">Advanced tofersen into the Phase 3 ATLAS study in presymptomatic SOD1-ALS patients</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="z2de37ad6320b46eeb351368de1b2ba71">
  <tr>
    <td style="width: 54pt;"></td>
    <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;">Roche reported tominersen data related to the dosing halt in the Phase 3 program</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="z911230fd2f144337a176cb370a6cad90">
  <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;">Mid-stage Pipeline: advancing multiple medicines with potential to change the standard of care for patients with severe diseases</div></td>
  </tr>
</table>
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  <tr>
    <td style="width: 54pt;"></td>
    <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;">Reported positive topline IONIS-PKK-L<sub>Rx</sub> results in patients with hereditary angioedema</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="z92b4354c4ad549a080cd8d010c521522">
  <tr>
    <td style="width: 54pt;"></td>
    <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;">Advanced ION373 into the Phase 2 portion of a pivotal study in patients with Alexander disease</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="ze82618f5d1874a02867e9c79478114b6">
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    <td style="width: 54pt;"></td>
    <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;">Advanced the IONIS-AGT-L<sub>Rx</sub> development program:</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;">&#9726;</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;">Reported positive </span>Phase 2 data in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">JACC: Basic to Translational Science</span></div></td>
  </tr>
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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;">Advanced into a </span>Phase 2b study in patients with hypertension uncontrolled with three or more antihypertensive medications</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="z6292e151336f4445a066e205041cfc07">
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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;">Advanced into a </span>Phase 2 study in patients with chronic heart failure with reduced injection fraction</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="z292711a914b2421fba09560c52cb853c">
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    <td style="width: 54pt;"></td>
    <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;">Advanced the ongoing Phase 2 study of ION541 in patients with ALS regardless of family history, resulting in a $10 million payment from Biogen</div></td>
  </tr>
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<div><br /></div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Business Segment</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. In October 2020, we acquired the remaining common stock of Akcea that we did not own and fully integrated Akcea&#8217;s operations into ours as of January 1, 2021.</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>30</span></div>
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<div></div>
</div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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 condensed consolidated financial statements in conformity with accounting principles generally accepted in the U.S. As such, we make certain estimates, judgments and assumptions that we believe are reasonable, based upon the information available to us. These judgments involve making estimates about the effect of matters that are inherently uncertain and may significantly impact our quarterly or annual results of operations and financial condition. Each quarter, our senior management reviews the development, selection and disclosure of such estimates with the audit committee of our board of directors. 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="z4ab8005523154308bf93e077c9a138a6">
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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;">Assessing the propriety of revenue recognition and associated deferred revenue;</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;">Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities; and</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;">In the first quarter of 2021, we determined the estimation of our income taxes was no longer a critical accounting estimate because we recorded a valuation allowance against the entirety of our net deferred tax assets in the fourth quarter of 2020. We recorded the expected impact from the valuation allowance on our tax provision for 2021.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There have been no other material changes to our critical accounting policies and estimates from the information provided in Item 7, &#8220;Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations&#8221; included in our Annual Report on Form 10-K for the year ended December 31, 2020.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Results of Operations</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue for the three months ended&#xA0;March 31, 2021 was $111.6 million compared to $133.4 million for the same period in 2020 and was comprised of the following (amounts in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z516eebf0865a4ea08c1619befa931779" 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>
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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;">&#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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  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div></td>
    <td 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>
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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>
    <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;">66.0</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;">TEGSEDI and WAYLIVRA revenue, 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;">19.8</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;">15.2</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: -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>
    <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;">4.6</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;">2.8</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div></td>
    <td 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;">84.4</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;">84.0</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D 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;">&#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: 76%;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization from upfront payments</div></td>
    <td 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;">20.1</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;">21.1</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%; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments</div></td>
    <td 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;">5.2</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;">&#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;">23.1</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; 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;">&#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;">1.9</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;">5.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D 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>
    <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;">27.2</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;">&#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;">49.4</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: 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;">&#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;">111.6</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;">133.4</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;">Our commercial revenue in the first quarter of 2021 was consistent with the same period last year. As we complete the transition of TEGSEDI operations in North America to Sobi, our commercial revenue from product sales will shift to distribution fee revenue.</div>
<div><br /></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 that can fluctuate depending on the timing of events. Our R&amp;D revenue decreased in the first quarter of 2021 compared to the same period in 2020 primarily because we earned more milestone payments in the first quarter of 2020 than in the first quarter of 2021. We anticipate our R&amp;D revenue to increase in the second half of 2021 compared to the first half of 2021 as many of our partnered programs advance.</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>31</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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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating Expenses</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="zf03ed8ef7ce744378ee42b0215df27be" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td 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;">159.0</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;">153.7</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;">Restructuring 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;">6.7</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;">&#8212;</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;">37.9</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;">40.8</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>
  </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;">203.6</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;">194.5</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: 24.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses, excluding non-cash compensation expense related to equity awards, for the three months ended&#xA0;March 31, 2021 increased compared to the same period in 2020. The increase was due to our investments in the Phase 3 program for IONIS-TTR-L<sub style="font-family: Times;">Rx</sub> and other medicines in our wholly owned pipeline. Additionally, we incurred approximately $7 million in costs related to the Akcea Acquisition and Restructured European Operations, primarily comprised of severance and retention costs. We expect our operating expenses, excluding <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">non-cash compensation expense related to equity awards,</span> to continue to increase during the rest of 2021 as we continue to advance our strategic priorities. Additionally, we expect to incur an additional $11 million to $14 million of restructuring costs, principally in the second quarter of 2021, related to our the Restructured North American TEGSEDI Operations to better align with the immediate needs of our business and to focus on our wholly owned pipeline. We also expect to recognize the majority of the remaining severance and retention costs related to the Akcea Acquisition and Restructured European Operations transactions in the second quarter of 2021. See Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Severance and Retention Costs</span>, for additional details.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To analyze and compare our results of operations to other similar companies, we believe it is important to exclude non-cash compensation expense related to equity awards from our operating expenses. We believe non-cash compensation expense related to equity awards is not indicative of our operating results or cash flows from our operations. Further, we internally evaluate the performance of our operations excluding it.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Cost of Sales</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales 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 sales 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 sales were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="ze67c8f2a34504d71b5d26127e9ad2f2a" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales, excluding non-cash compensation expense related to equity awards</div></td>
    <td 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;">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;"><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;">2.3</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;"><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;">0.2</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;">0.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total cost of sales</div></td>
    <td 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;">2.6</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>
    <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;">2.5</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>
  </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;">Our cost of sales</span>, excluding non-cash compensation expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were consistent with the same period in 2020.</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>32</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; 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="zacc453ce20fb4c009a44745862c7ddbd" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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: 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;">111.3</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;">91.4</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%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div></td>
    <td 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;">2.6</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;">&#8212;</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;">25.9</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;">25.6</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 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;">139.8</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;">117.0</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 were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z40e1dd84acd04b64b6a7871be75b13ec" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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: 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;">26.6</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;">18.4</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;">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;">6.3</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;">6.3</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;">32.9</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;">24.7</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Antisense drug discovery expenses</span>, excluding non-cash compensation expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> increased in the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in 2020 due to expenses we incurred related to advancing our research programs and investments we made to expand the reach of our antisense technology.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">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="z6eb87a43c7804717983573e6c9a2caf4" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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: 76%; background-color: #CCEEFF;"><div style="text-align: left; 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;">1.8</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;">4.3</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;">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;">0.6</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;">1.0</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;">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;">&#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;">13.3</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;">&#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;">5.9</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; 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;">1.4</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;">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: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION363</div></td>
    <td 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;">2.1</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;">&#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;">Other antisense development projects</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;">20.3</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%;">&#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;">21.0</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;">Development overhead 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;">22.5</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;">17.9</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;">Restructuring 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;">2.3</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;">&#8212;</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;">64.3</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;">&#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;">50.9</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;">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;">12.4</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;">11.8</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 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;">76.7</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>
    <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;">62.7</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="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>33</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: justify; text-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 development expenses</span>, excluding non-cash compensation expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> increased for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> primarily due to our broad Phase 3 program for IONIS-TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, which we initiated in late 2019. Additionally, we advanced other medicines in our wholly owned pipeline, including ION363, which we recently initiated a Phase 3 study for in patients with FUS-ALS.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may conduct multiple clinical trials on a drug candidate, including multiple clinical trials for the various indications we may be studying. Furthermore, as we obtain results from trials, we may elect to discontinue clinical trials for certain drug candidates in certain indications in order to focus our resources on more promising drug candidates or indications. Our Phase 1 and Phase 2 programs are clinical research programs that fuel our Phase 3 pipeline. When our medicines are in Phase 1 or Phase 2 clinical trials, they are in a dynamic state in which we may adjust the development strategy for each medicine. Although we may characterize a medicine as &#8220;in Phase 1&#8221; or &#8220;in Phase 2,&#8221; it does not mean that we are conducting a single, well-defined study with dedicated resources. Instead, we allocate our internal resources on a shared basis across numerous medicines based on each medicine&#8217;s particular needs at that time. This means we are constantly shifting resources among medicines. Therefore, what we spend on each medicine during a particular period is usually a function of what is required to keep the medicines progressing in clinical development, not what medicines we think are most important. For example, the number of people required to start a new study is large, the number of people required to keep a study going is modest and the number of people required to finish a study is large. However, such fluctuations are not indicative of a shift in our emphasis from one medicine to another and cannot be used to accurately predict future costs for each medicine. And, because we always have numerous medicines in preclinical and 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="text-align: justify; 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="zc0f5031e818648cd8697e8adb58f895f" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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: 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;">11.8</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;">12.0</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;">Restructuring 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;">0.3</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%;">&#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;">&#8212;</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;">3.1</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;">2.8</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>
  </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;">15.2</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;">14.8</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Manufacturing and development chemistry expenses</span>, excluding non-cash compensation expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were essentially flat for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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="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>
<div></div>
</div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on R&amp;D support expenses (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="z14e33d5123e347c5b0d0bcc51986e4b6" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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: 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;">4.3</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;">3.8</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;">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;">3.2</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;">2.4</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;">0.8</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;">0.7</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;">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;">0.8</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;">0.6</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;">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;">0.5</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;">0.6</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; 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;">1.3</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;">2.0</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 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;">10.9</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;">10.1</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; 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;">4.1</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;">4.6</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 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;">15.0</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;">14.7</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">R&amp;D support expenses</span>, excluding non-cash compensation expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> increased slightly compared to the same period in </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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="z8a6c455b8d7e4755b91849555db64a77" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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: 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;">45.3</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;">60.0</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%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div></td>
    <td 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;">4.1</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;">&#8212;</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total selling, general and administrative expenses, excluding non-cash compensation related to equity awards</div></td>
    <td 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;">49.4</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;">60.0</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%; 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;">11.8</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;">15.0</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 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;">61.2</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;">75.0</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>
  </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;">SG&amp;A expenses</span>, excluding non-cash compensation expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were lower for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>due to operating efficiencies attained from our integration of Akcea and our updated European distribution model. These decreases were slightly offset by restructuring costs related to the Akcea Acquisition and Restructured European Operations<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Investment Income</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment income for the three months ended&#xA0;March 31, 2021 was $4.6 million compared to $10.5 million for 2020. The decrease in investment income was primarily due to a decline in interest rates and a lower cash balance during the three months ended&#xA0;March 31, 2021 compared to the same period in 2020.</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>35</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;">Interest Expense</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 interest expense (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" id="ze2585a285c994b6fa0206fb3422f7f23" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</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;">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;">&#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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(as revised*)</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: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible 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 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;">0.9</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;">0.7</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;">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;">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;">0.9</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;">Interest on mortgage for primary R&amp;D and manufacturing facilities</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;">0.6</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;">0.6</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 interest expense</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;">2.4</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;">2.2</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>
<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="z72aae66caefb42779510fa04fbe52e2f">
  <tr>
    <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;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</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;">Income Tax Expense (Benefit)</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded negligible income tax expense for the three months ended&#xA0;March 31, 2021 primarily due to our valuation allowance and our expected taxable losses for the year. We recorded an income tax benefit of $3.1 million for the same period in 2020 primarily due to our pre-tax loss for the period and a $1.7 million tax benefit related to utilization of additional net operating loss carryforwards provided by the Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act, enacted by the U.S. Congress in March 2020.</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;">Net Loss</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 of $89.9 million for the three months ended&#xA0;March 31, 2021 compared to net loss of $49.9 million for the same period in 2020, which reflects the fluctuations discussed above.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Net Loss 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;">During the first quarter of 2020, we owned approximately 76 percent of Akcea. The shares of Akcea third parties owned represented an interest in Akcea&#8217;s equity that we did not control. However, because we maintained overall control of Akcea through our voting interest, we reflected Akcea&#8217;s results of operations in our condensed consolidated financial statements. We reflected the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock in a separate line called &#8220;Net loss attributable to noncontrolling interest in Akcea&#8221; on our statement of operations. Our noncontrolling interest in Akcea on our statement of operations for the three months ended March 31, 2020, was a loss of $10.3 million. After our acquisition of Akcea in October 2020, we no longer recorded any adjustment related to noncontrolling interest for Akcea&#8217;s net loss.</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;">Net Loss Attributable to Our Common Stockholders<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and Net 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 $89.9 million for the three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021 compared to net loss of $39.6 million for the same period in 2020. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Basic and diluted net loss per share for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were $</span>0.64<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Our basic and diluted net loss per share for the three months ended March 31, 2020 were $</span>0.28<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">We have financed our operations primarily from research and development collaborative agreements. We also finance our operations from commercial revenue from SPINRAZA royalties and TEGSEDI and WAYLIVRA commercial revenue. From our inception through March 31, 2021, we have earned approximately $5.1 billion 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 March 31, 2021, we have raised net proceeds of approximately $2.0 billion from the sale of our equity securities. Additionally, from our inception through March 31, 2021, we have borrowed approximately $1.5 billion under long-term debt arrangements to finance a portion of our operations.</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, including our cash, cash equivalents and short-term investments and debt obligations did not change significantly </span>at March 31, 2021 compared to December 31, 2020, except working capital. Our working capital increased because we reclassified a portion of our 1% Notes as a non-current liability on our condensed consolidated balance sheet in the first quarter of 2021.</div>
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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: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In April 2021, we issued $632.5 million of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes due in April 2026 and repurchased $247.9 million of our </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes. Therefore, as of March 31, 2021, we classified the repurchased portion of our </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">1%</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes as a non-current liability on our condensed consolidated balance sheet.</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 summarizes our contractual obligations as of March 31, 2021. 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="za13c169442c045db9a315d79ee77d037" 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 (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;">0.125% 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;">551.6</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">550.9</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: 64%;"><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%;">&#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;">313.0</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;">313.0</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;">&#8212;</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;">75.5</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;">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;">73.1</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: 64%;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating leases</div></td>
    <td 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;">22.4</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;">3.3</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%;">&#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;">19.1</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: 64%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations (principal and interest payable)</div></td>
    <td 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;">0.9</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;">0.1</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;">0.8</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>
  </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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">963.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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;">643.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
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<div><br /></div>
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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;">In April 2021, we repurchased $247.9 million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result, in April 2021, the remaining principal outstanding for our 1% Notes was $62.0 million. As a result of the repurchase, we reclassified the repurchased portion of our 1% Notes from current to non-current liabilities on our condensed consolidated balance sheet as of March 31, 2021 because we replaced this portion of our outstanding debt with long-term debt.</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 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 flows associated with our unrecognized tax benefits, we are unable to make reasonably reliable estimates of the period of cash settlement with the respective taxing authorities. Therefore, we have excluded our gross unrecognized tax benefits from our contractual obligations table above. We have not entered into, nor do we currently have, any off-balance sheet arrangements (as defined under SEC rules).</span></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;">Convertible Debt and Call Spread</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to our Convertible Debt and Call Spread accounting policies in Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, and Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible Debt</span>, in the Notes to our condensed consolidated financial statements for the significant terms of each convertible debt instrument.</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 March 31, 2021 for the purchase of services, capital equipment and materials as part of our normal course of business.</div>
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<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>
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    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 3.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK</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 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.</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 also exposed to changes in foreign currency exchange rates as we have foreign subsidiaries with functional currencies other than the U.S. dollar. </span>We translate our subsidiaries&#8217; functional currencies into our reporting currency, the U.S. dollar. As a result, our financial position, results of operations and cash flows can be affected by market fluctuations in the foreign currencies to U.S. dollar exchange rate,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>which are difficult to predict. A hypothetical 10 percent change in foreign exchange rates during any of the periods presented would not have had a material impact on our condensed consolidated financial statements.</div>
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    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 4.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONTROLS AND PROCEDURES</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 maintain disclosure controls and procedures 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 design 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 our most recently completed fiscal year and as of the end of the period covered by this Quarterly Report on Form 10-Q, we carried out an evaluation of the effectiveness of the design and operation of our disclosure controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, under the supervision 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 March 31, 2021. There have been no significant changes in our internal controls or in other factors that could significantly affect internal controls subsequent to March 31, 2021.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also performed an evaluation of any changes in our internal controls over financial reporting that occurred during our last fiscal quarter and that have materially affected, or are reasonably likely to materially affect, our internal controls over financial reporting. We conducted this evaluation under the supervision of and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer. That evaluation did not identify any changes in our internal controls over financial reporting that occurred during our latest fiscal quarter and that have materially affected, or are reasonably likely to materially affect, our internal controls over financial reporting.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART II &#8212; OTHER INFORMATION</div>
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    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 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-weight: bold;">LEGAL PROCEEDINGS</div></td>
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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;">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<sub>Rx</sub>. 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.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 not 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.</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-weight: bold;">RISK FACTORS</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;">Investing in our securities involves a high degree of risk. You should carefully consider the following information about the risks described below, together with the other information contained in this report and in our other public filings in evaluating our business. If any of the following risks actually occur, our business could be materially harmed, and our financial condition and results of operations could be materially and adversely affected. As a result, the trading price of our securities could decline, and you might lose all or part of your investment. We have marked with an asterisk those risk factors that reflect substantive changes from the risk factors included in our Annual Report on Form 10-K for the year ended December 31, 2020.</div>
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<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. Some of the principal risks related to our business include the following:</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: 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: 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>
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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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our and our partners&#8217; ability to compete effectively;</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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the availability of adequate coverage and payment rates for our medicines;</div></td>
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    <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>
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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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to successfully develop and obtain marketing approvals for our medicines;</div></td>
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    <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>
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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: 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>
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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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to protect our intellectual property;</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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to maintain the effectiveness of our personnel; and</div></td>
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    <td style="width: 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 other factors set forth below.</div></td>
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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>
<div><br /></div>
<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: 40.5pt; 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 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>
<div><br /></div>
<div style="text-align: justify; text-indent: 40.5pt; 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: 40.5pt; 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 physician and hospital policies that have been put in place as a result of the COVID-19 Pandemic restrict in-person access by third parties, which has in some cases impacted our commercialization efforts for TEGSEDI and WAYLIVRA. Additionally, Biogen has reported that as a result of the COVID-19 Pandemic, SPINRAZA sales revenues have decreased in part because 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. 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</div></td>
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<div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">and prioritizing COVID-19 patient care; and</div>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we have experienced some delays in necessary interactions with regulators, ethics committees and other</div></td>
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<div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">important agencies and contractors due to limitations in employee resources or forced furlough of</div>
<div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">government or contractor personnel.</div>
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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>
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<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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have limited experience as a company in commercializing medicines, and we 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. In addition, 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. We also will likely 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. Furthermore, we and our partners may not successfully commercialize additional medicines.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cost and effectiveness of our medicines compared to other available therapies;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">patient convenience of the dosing regimen for our medicines; and</div></td>
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    <td style="width: 18pt; vertical-align: top; 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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on the profile of our medicines, physicians, patients, patient advocates, payers or the medical community in general may not accept or use any medicines that we may develop.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, 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. 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. 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 mitigate 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 or our partner plan to have greater involvement with physicians and patients, if we or our partner cannot effectively maintain patients on TEGSEDI or WAYLIVRA, including due to limitations or restrictions on the ability to conduct periodic blood and urine monitoring of our patients as a result of the current COVID-19 Pandemic, we may not be able to generate substantial revenue from TEGSEDI or WAYLIVRA sales.</div>
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<div style="text-align: 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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our competitors engage in drug discovery throughout the world, are numerous, and include, among others, major pharmaceutical companies and specialized biopharmaceutical firms. Other companies are engaged in developing antisense technology. Our competitors may succeed in developing medicines that are:</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;">priced lower than our medicines;</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;">reimbursed more favorably by government and other third-party payers than our medicines;</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="zb95415600e494ca78e976c319ad26df9">
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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;">safer than our medicines;</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;">more effective than our medicines; or</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="z7d0662913f894e2a9c28950f2ced2460">
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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;">more convenient to use than our medicines.</div></td>
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<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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others, including our competitors, to treat 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>
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<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>
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<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>
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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;">Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;</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="zfc61f48badcf45539984ed4f0250b834">
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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;">Patisiran, tafamidis and tafamidis meglumine compete with TEGSEDI;</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;">Vutrisiran and acoramidis could compete with TEGSEDI and IONIS-TTR-L<sub style="font-family: Calibri;">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;">ARO-APOC3, lomitapide and gemcabene could compete with WAYLIVRA and IONIS-APOCIII-L<sub style="font-family: Calibri;">Rx</sub>; 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;">Arimoclomol, ultomiris, mastinib and trehalose could compete with tofersen and ION363.</div></td>
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<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>
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<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: justify; 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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain of our 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 IONIS-TTR-L<sub>Rx</sub>. We believe the enhancements we incorporated into IONIS-APOCIII-L<sub>Rx</sub> and IONIS-TTR-L<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 IONIS-TTR-L<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>
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<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>
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<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>
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<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>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in the U.S., TEGSEDI&#8217;s label contains a boxed warning for thrombocytopenia and glomerulonephritis;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI requires periodic blood and urine monitoring; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in the U.S., TEGSEDI is available only through a REMS program.</div></td>
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<div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prescription medicines may be promoted only for the approved 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>
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<div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, when approved, the FDA or a foreign regulatory authority may condition approval on the performance of post-approval clinical studies or patient monitoring, which could be time consuming and expensive. For example, in connection with the conditional marketing approval for WAYLIVRA in the EU, we are required to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. If the results of such post-marketing studies are not satisfactory, the FDA, EC or other foreign regulatory 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>
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<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 SPINRAZA, TEGSEDI and WAYLIVRA.</div>
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<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>
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<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>
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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;">fund our development activities for SPINRAZA;</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;">seek and obtain regulatory approvals for SPINRAZA; 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;">successfully commercialize SPINRAZA.</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 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: 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;">We are relying on third parties to market, sell and distribute 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;">We have entered into agreements with third parties to commercialize TEGSEDI and WAYLIVRA 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 April 2021, we entered into a distribution agreement with Sobi to commercialize TEGSEDI in the U.S. and Canada;</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we entered into a distribution agreement with Sobi to commercialize TEGSEDI and WAYLIVRA in Europe; and</div></td>
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    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, we granted PTC the exclusive right to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on Sobi and PTC to effectively market, sell and distribute TEGSEDI and WAYLIVRA and have less control over sales efforts and may receive less revenue than if we commercialized TEGSEDI or WAYLIVRA by ourselves. If Sobi or PTC does not successfully commercialize TEGSEDI or WAYLIVRA, including as a result of delays or disruption caused by the current COVID-19 Pandemic, we may receive limited revenue for TEGSEDI or WAYLIVRA in the U.S., Canada, Europe, Latin America or certain Caribbean countries, which could have a material adverse effect on our business, prospects, financial condition and results of operations.</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 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, or 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 placing limits on pharmaceutical price increases and tying 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 capping Medicare Part D beneficiary out-of-pocket pharmacy expenses) 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.</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: 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 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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<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="zad8dc31dbf7e4757b72c58d1ce10f8ab">
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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 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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<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="z6557d2e9ab054c78836a6cd88841f8d1">
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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 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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<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="z805f72b4846f4e3d9717cfc33eea2c19">
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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;">such authorities may disagree with the interpretation of data from preclinical or clinical studies;</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="ze71bd8674e0941c291817f74e3abd47f">
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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 find deficiencies in the manufacturing processes or facilities of third-party manufacturers who manufacture clinical and commercial supplies for our medicines, or may delay the inspection of such facilities due to restrictions related to the COVID-19 Pandemic; and</div></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="z525cc5fb757c4ef585d1bd9a9ec19087">
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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 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>
<div><br /></div>
<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;">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 or have been discontinued for other reasons. For example, in March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest Huntington&#8217;s disease based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded Independent Data Monitoring Committee. Similar results could occur in clinical studies for our other medicines, including the studies of tofersen, pelacarsen, IONIS-TTR-L<sub>Rx</sub>, IONIS-APOCIII-L<sub>Rx</sub> and ION363. If any of our medicines in clinical studies, including tofersen, pelacarsen, IONIS-TTR-L<sub>Rx</sub>, IONIS-APOCIII-L<sub>Rx</sub> and ION363, do not show sufficient efficacy in patients with the targeted indication, or if such studies are discontinued for any other reason, it could negatively impact our development and commercialization goals for these medicines and our stock price could decline.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even if our medicines are successful in preclinical and human clinical studies, the medicines may not be successful in late-stage clinical studies.*</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Successful results in preclinical or initial human clinical studies, including the Phase 2 results for some of our medicines in development, may not predict the results of subsequent clinical studies, including the studies of tofersen, pelacarsen, IONIS-TTR-L<sub>Rx</sub>, IONIS-APOCIII-L<sub>Rx</sub> and ION363. For example, in March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest Huntington&#8217;s disease based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded Independent Data Monitoring Committee. There are a number of factors that could cause a clinical study to fail or be delayed, including:</div>
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    <td style="width: 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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<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="z1a56bc91e4e246e9b48841b876cda3c5">
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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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<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="z456183c77ef441b086dbfbfa625affa5">
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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 or lack of efficacy in the trial;</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="z02da57c33d6a4aad82bc41cad6688483">
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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="zc2d369fb61e842b59ff70f3e9cb990e2">
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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, 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>
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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="zaf1f42d81e964083b6581efcfb40a508">
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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="z6f4a3f709d78438ca2160d63eb5871a7">
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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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<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="z880e5865d9c447baae005abf572130cf">
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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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<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="z01fda0d139004e7c89f95fa9153b6a69">
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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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    <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>
  </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 current COVID-19 Pandemic could make some of these factors more likely to occur.</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, 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>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any failure or delay in the clinical studies, including the studies of tofersen, pelacarsen, IONIS-TTR-L<sub>Rx</sub>, IONIS-APOCIII-L<sub>Rx</sub> and ION363, could reduce the commercial potential or viability of our medicines.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on third parties to conduct 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;">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 tofersen, pelacarsen, IONIS-TTR-L<sub>Rx</sub>, IONIS-APOCIII-L<sub>Rx</sub> and ION363. 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, 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, 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.</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: 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;">Roche for development and funding of tominersen;</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="zb1f576d84c1e45339b08305223201386">
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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;">Novartis for development and funding of pelacarsen; 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="z894c308ba5d148ad8d8032eba36c3db3">
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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>
  </tr>
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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>
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<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>
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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 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>
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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;">seek and obtain marketing authorizations; 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;">manufacture, market and sell our medicines.</div></td>
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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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    <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>
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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 higher-priority programs or change the focus of its own development programs; or</div></td>
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    <td style="width: 18pt; vertical-align: top; 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>
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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 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>
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<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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For planning purposes, we estimate and may disclose the timing of a variety of clinical, regulatory and other milestones, such as when we anticipate a certain medicine will enter clinical trials, when we anticipate completing a clinical study, or when we anticipate filing an application for, or obtaining, marketing authorization, or when we or our partners plan to commercially launch a medicine. We base our estimates on present facts and a variety of assumptions, many of which are outside of our control, including the 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-TTR-L<sub>Rx</sub>, IONIS-APOCIII-L<sub>Rx</sub> and ION363, the price of our securities could decrease.</div>
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<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>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our financial condition and business strategy</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.</div>
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<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 March 31, 2021, we had an accumulated deficit of approximately $1.2 billion and stockholders&#8217; equity of approximately $0.7 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 research grants and 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 medicines or achieve or sustain future profitability.</div>
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<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>
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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;">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 authorizations, preclinical activities and commitment of significant additional resources prior to their successful commercialization. These activities will require significant cash. As of </span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we had cash, cash equivalents and short-term investments equal to $</span>1.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 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:</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;">successful commercialization of SPINRAZA, TEGSEDI and WAYLIVRA;</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;">additional marketing approvals for WAYLIVRA and TEGSEDI;</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="z2eba9e4b9e6a40e8b01b1cf9c73f7730">
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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 profile and launch timing of our medicines, including TEGSEDI and WAYLIVRA;</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;">changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;</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="z6b0174dcb24c49409fd39e5712e1dcf6">
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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;">continued scientific progress in our research, drug discovery and development programs;</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 size of our programs and progress with preclinical and 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;">the time and costs involved in obtaining marketing authorizations; 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;">competing technological and market developments, including the introduction by others of new therapies that address our markets.</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we need additional funds, we may need to raise them through public or private financing. Additional financing may not be available 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>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our intellectual property</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we cannot protect our patent rights or our other proprietary rights, others may compete more effectively against us.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our success depends to a significant degree upon whether we can continue to develop, secure and maintain intellectual property rights to proprietary products and services. However, we may not receive issued patents on any of our pending patent applications in the U.S. or in other countries and we may not be able to obtain, maintain or enforce our patents and other intellectual property rights which could impact our ability to compete effectively. In addition, the scope of any of our issued patents may not be sufficiently broad to provide us with a competitive advantage. Furthermore, other parties may successfully challenge, invalidate or circumvent our issued patents or patents licensed to us so that our patent rights do not create an effective competitive barrier or revenue source.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot be certain that the U.S. Patent and Trademark Office, or U.S. PTO, and courts in the U.S. or the patent offices and courts in foreign countries will consider the claims in our patents and applications covering 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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or any licensor partner loses or cannot obtain patent protection for SPINRAZA, TEGSEDI, WAYLIVRA, or any of our other medicines in development, it could have a material adverse impact on 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;">Intellectual property litigation could be expensive and prevent us from pursuing our programs.</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 have to defend our intellectual property rights. If we are involved in an intellectual property dispute, we may need to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. PTO or the International Trade Commission or foreign patent authorities. Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If a third-party claims that our medicines or technology infringe its patents or other intellectual property rights, we may have to discontinue an important product or product line, alter our products and processes, pay license fees or cease certain activities. We may not be able to obtain a license to needed intellectual property on favorable terms, if at all. There are many patents issued or applied for in the biotechnology industry, and we may not be aware of patents or patent applications held by others that relate to our business. This is especially true since patent applications in the U.S. are filed confidentially for the first 18 months. Moreover, the validity and breadth of biotechnology patents involve complex legal and factual questions for which important legal issues remain.</div>
<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 business strategy and personnel</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 fail to successfully integrate Akcea&#8217;s business and operations, it may adversely affect our future results.</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 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 medicines, 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>
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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;">failure to successfully manage relationships with partners, customers, distributors and suppliers;</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;">disruptions to Akcea&#8217;s commercial operations;</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="zc4b70658474a45e0bd1e47c4d4847687">
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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;">potential incompatibility of technologies and systems;</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;">failure to leverage the capabilities of the combined company quickly and effectively;</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;">potential difficulties integrating and harmonizing business systems and processes;</div></td>
  </tr>
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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;">tax benefits of the combined structure may not be available or in the expected amounts; 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 loss of key employees.</div></td>
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<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>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2020, Dr. Crooke, our founder and Chief Executive Officer, transitioned from Chief Executive Officer to Executive Chairman of our Board of Directors. Following the 2021 Annual Meeting of Stockholders, Dr. Crooke will step down from the Board and will serve as a Strategic Advisor to the Company, providing strategic advice and continuing to participate in the Company&#8217;s scientific activities. Starting in January 2020, Dr. Monia, who had been our Chief Operating Officer for the last year and has been a member of our team since our founding over 30 years ago, serves as our Chief Executive Officer. If this transition is not successful, our business could suffer.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The loss of key personnel, or the inability to attract and retain highly skilled personnel, could make it more difficult to run our business and reduce our likelihood of success.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are dependent on the principal members of our management and scientific staff. 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, we are dependent on the principal members of our staff responsible for marketing, sales and distribution activities. If we are not able to recruit and retain qualified </span>marketing and sales personnel, the sales of TEGSEDI and WAYLIVRA may be adversely affected.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to taxes</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our ability to use our net operating loss carryovers and certain other tax attributes may be limited.*</div>
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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;">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, and we do not expect that it will materially impact our 2021 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 are 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 is 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. In addition, at the state level, there may be periods during which the use of net operating losses is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our future taxable income could be impacted by changes in tax laws, regulations and treaties.</div>
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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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 </span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the market price of our common stock ranged from $</span>64.37<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to $</span>41.42<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 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.</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 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In April 2021, we completed a $632.5 million offering of 0% Notes. </span>In December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our existing 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. Additionally, in connection with the pricing of our 0% Notes and 0.125% Notes, we entered into call spread transactions in which we purchased note hedges and sold warrants. <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 18.4 million shares of our common stock upon conversion of our 0% Notes, 0.125% Notes, and 1% Notes, up to 10.9 million shares in connection with the warrant transactions we entered into in connection with the issuance of our 0% Notes, and up to 6.6 million shares in connection with the warrant transactions we entered into in connection with the issuance of our 0.125% Notes, in each case subject to customary anti-dilution adjustments. The addition of any of these shares into the public market may have an adverse effect on the price of our securities.</div>
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<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>52</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, pursuant to the call spread transactions we entered into in connection with the pricing of our 0% Notes and 0.125% Notes, the counterparties are likely to modify their hedge positions from time to time at or prior to the conversion or maturity of the notes by purchasing and selling shares of our common stock, other of our securities, or other instruments, including over-the-counter derivative instruments, that they may wish to use in connection with such hedging, which may have a negative effect on the conversion value of those notes and an adverse impact on the trading price of our common stock. The call spread transactions are expected generally to reduce potential dilution to holders of our common stock upon any conversion of our 0% Notes or 0.125% Notes or offset any cash payments we are required to make in excess of the principal amount of the converted 0% Notes or 0.125% Notes, as the case may be. However, the warrant transactions could separately have a dilutive effect to the extent that the market value per share of our common stock exceeds the applicable strike price of the warrants.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The SEC and other regulators have continued to adopt new rules and regulations and make additional changes to existing regulations that require our compliance. 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>
<div><br /></div>
<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>
<div><br /></div>
<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: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span>54</span></div>
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<div style="text-align: justify; margin-bottom: 12pt; 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.</div>
<div style="text-align: justify; text-indent: 36pt; margin-bottom: 12pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our U.S. operations, we are commercializing TEGSEDI in the EU, Canada, Latin America and certain Caribbean countries, and WAYLIVRA in the EU, Latin America and certain Caribbean countries. We face risks associated with our international operations, including possible unfavorable regulatory, pricing and reimbursement, political, tax and labor conditions, which could harm our business. Because we have international operations we are subject to numerous risks associated with international business activities, including:</div>
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    <td style="width: 18pt; vertical-align: top; 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>
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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;">complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;</div></td>
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    <td style="width: 18pt; vertical-align: top; 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>
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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 certain circumstances, increased dependence on the commercialization efforts and regulatory compliance of third-party distributors or strategic partners;</div></td>
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    <td style="width: 18pt; vertical-align: top; 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>
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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;">U.S. and foreign government tariffs, trade restrictions, price and exchange controls and other 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;">anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;</div></td>
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    <td style="width: 18pt; vertical-align: top; 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;">economic weakness, including inflation, natural disasters, war, events of terrorism, political instability or public health issues or pandemics, such as the current COVID-19 Pandemic, in particular foreign countries or globally;</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;">fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenue, and other obligations related to doing business in another country;</div></td>
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    <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>
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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;">workforce uncertainty in countries where labor unrest is more common than in the U.S.; and</div></td>
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    <td style="width: 18pt; vertical-align: top; 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>
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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="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 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>
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    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 2.</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS</div></td>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
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    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 3.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">DEFAULT UPON SENIOR SECURITIES</div></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
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    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 4.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">MINE SAFETY DISCLOSURES</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;">Not applicable.</div>
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    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 5.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">OTHER INFORMATION</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;">Not applicable.</div>
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    <td style="width: 72pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 6.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">EXHIBITS</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;">a.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exhibits</div></td>
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    <td style="width: 12.69%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit Number</div></td>
    <td style="width: 2.06%; vertical-align: top;">&#160;</td>
    <td style="width: 85.25%; 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;">Description of Document</div></td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; 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;&#160;</span><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036121010402/brhc10022399_ex3-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.1</a></div></td>
    <td style="width: 2.06%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amended and Restated Bylaws, filed as an exhibit to Registrant&#8217;s Form 8-K filed with the SEC on March 29, 2021 and incorporated herein by reference.</div></td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.06%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1</div></td>
    <td style="width: 2.06%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Letter agreement dated October 21, 2020 to the License Agreement by and among Akcea Therapeutics, Inc. and Pfizer Inc. dated October 4, 2019. Portions of this exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.</div></td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.06%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.2</div></td>
    <td style="width: 2.06%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Board Compensation Policy.</div></td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.06%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036121010402/brhc10022399_ex14-1.htm">14.1</a></div></td>
    <td style="width: 2.06%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
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  <tr>
    <td style="width: 12.69%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.06%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.1</div></td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.06%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.2</div></td>
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  </tr>
  <tr>
    <td style="width: 12.69%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.06%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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  <tr>
    <td style="width: 12.69%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">32.1</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div></td>
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    <td style="width: 85.25%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.</div></td>
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  <tr>
    <td style="width: 12.69%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.06%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101</div></td>
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    <td style="width: 12.69%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 2.06%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 85.25%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
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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; font-weight: bold;">SIGNATURES</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the Registrant and in the capacities and on the dates indicated.</div>
<div><br /></div>
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    <td style="width: 17.72%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">May 5, 2021</div></td>
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    <td style="width: 50.36%; vertical-align: top;">&#160;</td>
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    <td style="width: 50.36%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Finance and Chief Financial Officer</div></td>
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<DOCUMENT>
<TYPE>EX-10.1
<SEQUENCE>2
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<DESCRIPTION>EXHIBIT 10.1
<TEXT>
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      <div style="font-family: 'Times New Roman',Times,serif; text-align: right;"><font style="font-weight: bold;">Exhibit 10.1</font><br>
      </div>
      <font style="font-family: 'Times New Roman',Times,serif;"><br>
      </font>
      <div style="font-family: 'Times New Roman',Times,serif; text-align: justify;"> <font style="font-weight: bold;">CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS EXHIBIT BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) WOULD BE COMPETITIVELY
          HARMFUL IF PUBLICLY DISCLOSED. SUCH EXLUDED INFORMATION HAS BEEN MARKED WITH "[***]".</font><br>
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      <div style="font-family: 'Times New Roman',Times,serif;"> <br>
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      <div style="font-family: 'Times New Roman',Times,serif;"> <br>
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      <div style="font-family: 'Times New Roman',Times,serif;">October 21, 2020</div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="font-family: 'Times New Roman',Times,serif;">Pfizer Inc.</div>
      <div style="font-family: 'Times New Roman',Times,serif;">235 East 42<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">nd</sup> Street</div>
      <div style="font-family: 'Times New Roman',Times,serif;">New York, NY&#160; 10017</div>
      <div style="font-family: 'Times New Roman',Times,serif;">Attention: James Rusnak, M.D., Ph.D.</div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z5ceab468d510420ebe179641063a23c3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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            <td style="width: 36pt; vertical-align: top; font-family: 'Times New Roman',Times,serif; font-weight: bold;">Re:</td>
            <td style="width: auto; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
              <div style="font-weight: bold;">AKCEA-ANGPTL3-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> License Agreement</div>
            </td>
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      <div style="font-family: 'Times New Roman',Times,serif;"><br>
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      <div style="font-family: 'Times New Roman',Times,serif;">Dear Dr. Rusnak:</div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman',Times,serif;">This letter agreement (&#8220;<font style="font-weight: bold; font-style: italic;">Letter Agreement</font>&#8221;) is in reference to the License Agreement (the &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;), dated October 4, 2019, by and between Akcea Therapeutics, Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Akcea</font>&#8221;) and Pfizer Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Pfizer</font>&#8221;). Any capitalized terms not defined in this Letter Agreement will have the meanings set forth in the Agreement, unless expressly specified otherwise.</div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">1.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160; &#160;&#160; &#160;&#160; <u>Akcea&#8217;s Right to Participate in Funding of Development
            of the Product</u>.&#160; Akcea and Pfizer desire to modify <u>Section 2.3.4</u> of the Agreement. Accordingly, <u>Section 2.3.4</u> of the Agreement is deleted in its entirety and replaced with the following provision:</font></div>
      <div style="font-family: 'Times New Roman',Times,serif;">&#160;</div>
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            <td style="width: 36pt; vertical-align: top; font-family: 'Times New Roman',Times,serif;"><a name="z_Ref16859526"></a><a name="z_Ref18959769"></a><font style="font-weight: bold;">2.3.4</font></td>
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              <div style="font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif; font-weight: bold;"><u>Akcea&#8217;s Right to Participate in the Funding of Development of the
                    Product</u></font><font style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">. At any time beginning on the Closing Date until&#160; [***], Akcea will have the conditional right to elect to participate in the funding of the
                  Development of the Product with Pfizer under the Development Plan pursuant to this <u>Section 2.3.4</u>. If Akcea provides written notice of such election to Pfizer prior to [***] (a &#8220;<font style="font-weight: bold; font-style: italic;">Notice


                    of Interest</font>&#8221;), then the Parties will negotiate in good faith the terms and conditions of Akcea&#8217;s participation in the funding of the Development of the Product with Pfizer under the Development Plan for a period of [***],
                  including certain [***] terms for [***]. If Akcea (a) gives notice that it does not wish to participate in the funding of the Development of the Product with Pfizer under the Development Plan, (b) fails to give a timely Notice of
                  Interest, or (c) gives a timely Notice of Interest but the Parties cannot mutually agree on the terms upon which Akcea will participate in the funding of the Development of the Product with Pfizer under the Development Plan by the [***]
                  following the delivery of such notice, then (i) Akcea&#8217;s right to participate in the funding of the Development of the Product with Pfizer under the Development Plan pursuant to this <u>Section 2.3.4</u> will automatically terminate, and
                  (ii) Pfizer will continue to be solely responsible for the Development of the Product, including all funding, in accordance with the Development Plan.</font></div>
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      <div style="text-align: justify; text-indent: 0pt; margin-left: 72pt; font-family: 'Times New Roman',Times,serif;">For purposes of this <u>Section 2.3.4</u>, [<a name="z_Hlk52887297"></a>***].</div>
      <div style="font-family: 'Times New Roman',Times,serif;">&#160;</div>
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                    <div style="text-align: left; font-family: 'Times New Roman',Times,serif;">October 21, 2020</div>
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                  <div><font id="DSPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">Page 2</font> <br>
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      <div style="text-align: justify; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">2.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; This Letter Agreement may be executed in any number of
          counterparts, each of which shall be deemed an original and all of which taken together shall be deemed to constitute one and the same agreement. The Parties agree that execution of this Letter Agreement by industry standard electronic signature
          software and/or by exchanging executed signature pages in .pdf format via e-mail shall have the same legal force and effect as the exchange of original signatures, and that in any proceeding arising under or related to this Letter Agreement, each
          Party hereby waives any right to raise any defense or waiver based upon execution of this Letter Agreement by means of such electronic signatures or maintenance of the executed agreement electronically.</font></div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
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      <div style="text-align: justify; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">3.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160; &#160;&#160; &#160;&#160;&#160;&#160; Except as otherwise expressly set forth in this Letter
          Agreement, the Agreement remains in full force and effect in accordance with its terms.</font></div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
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      <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-size: 12pt; font-style: italic;"><font style="font-size: 10pt; font-weight: bold;">[</font><font style="font-size: 10pt;">Signature page to follow<font style="font-weight: bold;">]</font></font></div>
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                    <div style="text-align: left; font-family: 'Times New Roman',Times,serif;">October 21, 2020</div>
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      <div style="text-indent: 40.3pt; font-family: 'Times New Roman',Times,serif;">If the terms of this Letter Agreement are acceptable, please so indicate by executing a copy of this Letter Agreement and returning it to Akcea.</div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="font-family: 'Times New Roman',Times,serif;">Very truly yours,</div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">AKCEA THERAPEUTICS, INC.</div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="font-family: 'Times New Roman',Times,serif;"><u>/s/Damien McDevitt</u></div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="font-family: 'Times New Roman',Times,serif;">Damien McDevitt, Ph.D.</div>
      <div style="font-family: 'Times New Roman',Times,serif;">Chief Executive Officer</div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="font-family: 'Times New Roman', Times, serif; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;"><u>AGREED TO AND CONFIRMED BY PFIZER INC.</u></font><font style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">:</font></div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="font-family: 'Times New Roman',Times,serif;">By: <u>/s/James Rusnak</u></div>
      <div style="font-family: 'Times New Roman',Times,serif;">Name: James Rusnak</div>
      <div style="font-family: 'Times New Roman',Times,serif;">Title: SVP, Chief Development Officer</div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </div>
      <div style="font-family: 'Times New Roman',Times,serif;"><br>
      </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;"><font style="font-family: 'Times New Roman',Times,serif;"></font></div>
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</DOCUMENT>
<DOCUMENT>
<TYPE>EX-10.2
<SEQUENCE>3
<FILENAME>ex10_2.htm
<DESCRIPTION>EXHIBIT 10.2
<TEXT>
<html>
  <head>
    <title></title>
    <!-- Licensed to: Ionis
         Document created using EDGARfilings PROfile 7.4.0.0
         Copyright 1995 - 2021 Broadridge -->
  </head>
<body style="font-family: 'Times New Roman'; font-size: 10pt; text-align: left; color: #000000;" bgcolor="#ffffff">
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    <hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade">
    <div style="text-align: right;"><font style="font-weight: bold;">Exhibit 10.2</font><br>
    </div>
    <div> <br>
    </div>
    <div>
      <div style="text-align: right; font-style: italic;">Adopted by the Board of Directors March 26, 2021</div>
      <div><br>
      </div>
      <div style="text-align: center; color: rgb(0, 0, 0); font-weight: bold;">Non-Employee Director Compensation Policy</div>
      <div><br>
      </div>
      <div style="color: rgb(0, 0, 0);">Ionis Pharmaceuticals, Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;) values the contributions made by its Board of Directors.&#160; In recognition of these valuable contributions, Ionis will
        provide each non-employee Director with the compensation described in this policy.</div>
      <div><br>
      </div>
      <div style="color: rgb(0, 0, 0); font-weight: bold;"><u>Cash Compensation</u></div>
      <div>&#160;</div>
      <div style="color: rgb(0, 0, 0);">Each non-employee Director will receive cash compensation based on his or her role on the Board and Board committees as follows:</div>
      <div style="color: rgb(0, 0, 0);"> <br>
      </div>
      <table id="z1717d93b81bc485884d54a0148124607" 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: 72%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;"><a name="z_Hlk512004434"></a>Role</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Cash Compensation</div>
            </td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div>Board Member (base retainer)</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$60,000<sup style="font-weight: bold; vertical-align: text-top; line-height: 1; font-size: smaller;">(1)</sup></div>
            </td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>Non-Executive Chairman of the Board (additional)</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$40,000</div>
            </td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div>Independent Lead Director (additional)</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">$40,000</div>
            </td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">
              <div>Committee Chair (additional):</div>
            </td>
            <td style="width: 28%; vertical-align: top; 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"><br>
            </td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
              <div style="margin-left: 9pt;">-Audit</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center; background-color: rgb(204, 238, 255);" rowspan="1">$24,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">
              <div style="margin-left: 9pt;">-Commercial Compliance</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">$10,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
              <div style="margin-left: 9pt;">-Compensation</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
              <div style="text-align: center;">$20,000</div>
            </td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">
              <div style="margin-left: 9pt;">-Finance</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">$20,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
              <div style="margin-left: 9pt;">-Nominating, Governance and Review</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center; background-color: rgb(204, 238, 255);" rowspan="1">$20,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">
              <div style="margin-left: 9pt;">-Science/Medical</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">$20,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
              <div>Committee Member (additional):</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center; background-color: rgb(204, 238, 255);" rowspan="1"><br>
            </td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">
              <div style="margin-left: 9pt">-Audit</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">$12,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
              <div style="margin-left: 9pt">-Commercial Compliance</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center; background-color: rgb(204, 238, 255);" rowspan="1">$5,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">
              <div style="margin-left: 9pt">-Compensation</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">$10,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
              <div style="margin-left: 9pt">-Finance</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center; background-color: rgb(204, 238, 255);" rowspan="1">$10,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">
              <div style="margin-left: 9pt">-Nominating, Governance and Review</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">$10,000</td>
          </tr>
          <tr>
            <td style="width: 72%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
              <div style="margin-left: 9pt">-Science/Medical</div>
            </td>
            <td style="width: 28%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center; background-color: rgb(204, 238, 255);" rowspan="1">&#160;$10,000</td>
          </tr>

      </table>
      <div><font style="color: rgb(0, 0, 0);"> </font><br>
      </div>
      <table id="zd9f4cd58448442cdb2cf0ffb54103389" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 18pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top; color: rgb(0, 0, 0);">(1)</td>
            <td style="width: auto; vertical-align: top;">
              <div style="color: rgb(0, 0, 0);">Before March 31, 2024 this annual base cash retainer for each non-employee Director (not including fees for Non-Executive Chair, Independent Lead Director, Committee Chair or Committee Member) is limited to a
                maximum of $70,000 per year.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="color: rgb(0, 0, 0); font-weight: bold;"><u>Equity Compensation</u></div>
      <div style="color: rgb(0, 0, 0); font-weight: bold;"><u> <br>
        </u></div>
      <div style="color: rgb(0, 0, 0);">Each non-employee Director will receive an initial stock option award and restricted stock unit award upon joining the Board and an annual stock option award and restricted stock unit award for each year of continued
        service as follows (subject to the aggregate grant date value limit described below):</div>
      <div><font style="color: rgb(0, 0, 0);"> </font><br>
      </div>
      <table id="zbf5acf06abd5462c89ec5419af8b712f" 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: 75%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Type of Grant</div>
            </td>
            <td style="width: 25%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: center; font-weight: bold;">Number of Shares*</div>
            </td>
          </tr>
          <tr>
            <td style="width: 75%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div>Initial Stock Option Grant</div>
            </td>
            <td style="width: 25%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">24,000</div>
            </td>
          </tr>
          <tr>
            <td style="width: 75%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>Initial Restricted Stock Unit Grant</div>
            </td>
            <td style="width: 25%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">10,667</div>
            </td>
          </tr>
          <tr>
            <td style="width: 75%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div>Annual Stock Option Grant</div>
            </td>
            <td style="width: 25%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">12,000</div>
            </td>
          </tr>
          <tr>
            <td style="width: 75%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div>Annual Restricted Stock Unit Grant</div>
            </td>
            <td style="width: 25%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">5,333</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div>
        <div style="color: rgb(0, 0, 0);">*These equity awards are to be automatically granted pursuant to the terms of the Ionis Pharmaceuticals, Inc.&#160;Amended and Restated 2002 Non-Employee Directors Stock Option Plan as approved by our stockholders on
          June 4, 2020 (the <font style="font-weight: bold; font-style: italic;">&#8220;NED Plan&#8221;</font>).&#160; Notwithstanding the terms of the NED Plan, (1) the Compensation Committee, with input from its independent consultant, may reduce the number of shares to
          be automatically issued on a grant date for each such award so that the awards granted have an aggregate grant date fair value (as determined in accordance with FASB Topic ASC 718 or its successor) that is aligned with the set of peer companies
          the Compensation Committee uses to evaluate compensation, and (2) the initial equity awards for new directors will be adjusted downward such that they are 1.5X the annual equity awards for any given year.</div>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">1</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>
      <div style="text-align: right; font-style: italic;">Adopted by the Board of Directors March 26, 2021</div>
      <div><br>
      </div>
      <div style="color: rgb(0, 0, 0);">The exercise price of each stock option will be the Fair Market Value (as defined in the NED Plan) of Ionis&#8217; common stock on the date of grant.</div>
      <div style="color: rgb(0, 0, 0);"> <br>
      </div>
      <div>As set forth in the NED Plan, initial grants vest on the annual anniversary of the date of grant and annual grants <font style="color: rgb(0, 0, 0);">vest on either (1) the annual anniversary of the date of grant, </font><a name="z_Hlk33442155"></a><font style="color: rgb(0, 0, 0);">or (2) the next regularly scheduled annual meeting of stockholders, whichever occurs earlier</font><a name="z_Hlk30518567"></a><font style="color: rgb(0, 0, 0);">.</font></div>
      <div><font style="color: rgb(0, 0, 0);"> <br>
        </font></div>
      <div style="text-align: justify;">While serving on the Board, each non-employee Director may not sell Ionis shares obtained pursuant to vesting of restricted stock unit awards if selling such shares would reduce the shares owned by such non-employee
        Director (not including stock options or unvested restricted stock units) below an amount that is equal to four times his or her annual base cash retainer.<br>
        <br>
      </div>
      <div style="color: rgb(0, 0, 0); font-weight: bold;"><u>Review of Non-Employee Director Compensation Policy</u></div>
      <div><br>
      </div>
      <div style="color: rgb(0, 0, 0);">This policy will be reviewed annually by Ionis&#8217; Compensation Committee and Board of Directors.</div>
      <div style="color: rgb(0, 0, 0);"> <br>
      </div>
      <div style="color: rgb(0, 0, 0);">On at least an annual basis, Ionis will retain an independent consultant to (1) advise the Compensation Committee on recent developments and best practices concerning director compensation, and (2) compare Ionis&#8217;
        director compensation levels, policies, practices, and procedures to a set of peer companies selected by the Compensation Committee with input from the independent consultant.</div>
      <div><br>
      </div>
      <div style="color: rgb(0, 0, 0);">Ionis reserves the right to amend this compensation policy at any time so long as the issuance of the equity awards comply with the terms of the NED Plan or any successor thereto.</div>
      <div style="color: rgb(0, 0, 0);"> <br>
      </div>
      <div style="color: rgb(0, 0, 0);"> <br>
      </div>
      <div style="text-align: center; color: rgb(0, 0, 0);"> <font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">2</font></div>
      <div style="color: rgb(0, 0, 0);">
        <hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"> </div>
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</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>4
<FILENAME>ex31_1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis
         Document created using EDGARfilings PROfile 7.4.0.0
         Copyright 1995 - 2021 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:956881ca-11d1-4726-85b7-68a37548513a"><div style="text-align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></font>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="z075db8fceff74dc48a630e5cc4b86640"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I have reviewed this Quarterly Report on Form 10-Q 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="zd97fe935d59247d08571e540b7b0bc2b"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, this quarterly 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 quarterly 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="z122986904ccd4b9182d6973805568222"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, the condensed consolidated financial statements, and other financial information included in this quarterly report, fairly present in all material respects the financial condition, condensed consolidated results of operations and condensed consolidated cash flows of the registrant as of, and for, the periods presented in this quarterly 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="z199f72406d9e427996e3148db4019a52"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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="zf87d973ef35b416ea1444c37f67d1e0c"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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; 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color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z3f76252bf71c4f90a3768f06773cb940"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">c)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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="zc3e611580ccb4381b395c4e14e6116a6"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">d)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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; 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="z39bac1d605154f319ebe019d8c23cc44"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The registrant&#8217;s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant&#8217;s auditors and the audit committee of registrant&#8217;s board of directors (or persons performing the equivalent functions):</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z1932892976e54ec580f8171b51abcbb0"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</td><td style="width: auto; 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color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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="z7e6b97b3911f4a52a4517053aeee61d2"><tr><td style="width: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated: May 5, 2021</div></td><td style="width: 72.25%; 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: 27.75%; 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: 72.25%; 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MONIA</div></td><td style="width: 72.25%; 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: 27.75%; 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: 72.25%; 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: 27.75%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Executive Officer</div></td><td style="width: 72.25%; 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 style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></div></div></body></html>
</TEXT>
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<DOCUMENT>
<TYPE>EX-31.2
<SEQUENCE>5
<FILENAME>ex31_2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
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  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:9770b480-fdae-48ad-8dab-7c414e81bcac"><div style="text-align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></font>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="zf78881497cd14e5fad5ca219b9891950"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I have reviewed this Quarterly Report on Form 10-Q 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="za1db5fb832814b7297f743cb49d16016"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, this quarterly 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 quarterly 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="za687ee72ed5a45e39765c795e4ac14d3"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, the condensed consolidated financial statements, and other financial information included in this quarterly report, fairly present in all material respects the financial condition, condensed consolidated results of operations and condensed consolidated cash flows of the registrant as of, and for, the periods presented in this quarterly 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="zcd11c0a7bf4840da89796037c9027ae0"><tr><td style="width: 18pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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="z3209ccd757a941fa8bde86394400f861"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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; 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color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z4bb633ccd8514fa5aedd8fe1ff9cd726"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">c)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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="zaa02373855e14adc87f987e0cd8f6fce"><tr><td style="width: 36pt;"></td><td style="width: 18pt; 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font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zb5a0a66cc0084b37b06eb87599c18636"><tr><td style="width: 39.27%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a name="z3a893fc63bc44c8c8146b8729339adbf"><!--Anchor--></a>Dated: May 5, 2021</div></td><td style="width: 60.73%; 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: 39.27%; 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: 60.73%; 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: 39.27%; 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: 60.73%; 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: 39.27%; 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: 60.73%; 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: 39.27%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Financial Officer</div></td><td style="width: 60.73%; 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></div></div></body></html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
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  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:3d169df3-22e7-43e5-8644-a48762b313e4"><div style="text-align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><font style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></font>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 Section 906 of the Sarbanes-Oxley Act of 2002, Brett P. Monia, the Chief Executive Officer of Ionis Pharmaceuticals, Inc., (the &#8220;Company&#8221;), and Elizabeth L. Hougen, the Chief Financial Officer of the Company, each hereby certifies that, to the best of his or her knowledge:</div><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z24bd75b88cfc4c059c6842deb729dcee"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The Company&#8217;s Quarterly Report on Form 10-Q for the period ended March 31, 2021, to which this Certification is attached as Exhibit 32.1 (the &#8220;Periodic Report&#8221;), fully complies with the requirements of Section 13(a) or Section 15(d) of the Securities Exchange Act of 1934, as amended; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z15e4821616f84fd09a60db59d839ef23"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; align: right; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The information contained in the Periodic Report fairly presents, in all material respects, the financial condition of the Company at the end of the period covered by the Periodic Report and the results of operations of the Company for the period covered by the Periodic Report.</div></td></tr></table><div><br></div><div><br></div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zd41c5d2ab9b74862aecc7c99ad561252"><tr><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a name="z67c7d4b1a5524f7095e3a56b8ca645e7"><!--Anchor--></a>Dated: May 5, 2021</div></td><td style="width: 2%; 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: 49%; 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: 49%; 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: 2%; 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: 49%; 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: 49%; 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: 2%; 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: 49%; 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></tr><tr><td style="width: 49%; 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: 2%; 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: 49%; 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></tr><tr><td style="width: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Executive Officer</div></td><td style="width: 2%; 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: 49%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Financial Officer</div></td></tr></table><div><br></div><div style="text-align: justify; text-indent: 36pt; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A signed original of this written statement required by Section 906 has been provided to Ionis Pharmaceuticals, Inc. and will be retained by Ionis Pharmaceuticals, Inc. and furnished to the Securities and Exchange Commission or its staff upon request.</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></div></div></body></html>
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<DOCUMENT>
<TYPE>EX-101.CAL
<SEQUENCE>8
<FILENAME>ions-20210331_cal.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION CALCULATION LINKBASE
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<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>10
<FILENAME>ions-20210331_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
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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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiability_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl">Deferred revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiability_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl1">Contract with Customer, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl1" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl1" />
    <link:loc xlink:type="locator" xlink:href="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/verboseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl">Current portion of deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1">Contract with Customer, Liability, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="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/verboseLabel" 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_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/terseLabel" xlink:title="us-gaap_ConvertibleDebtCurrent_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebtCurrent_lbl">Current portion of 1 percent convertible senior notes, net</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/label" xlink:title="us-gaap_ConvertibleDebtCurrent_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtCurrent_lbl1">1 percent convertible senior notes, net</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: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, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl1">Convertible 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_lbl1" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl1" />
    <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/terseLabel" xlink:title="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xlink:title="label: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1">Convertible Notes Payable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xlink:title="label: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="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/terseLabel" 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:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock_lbl1">Convertible Debt [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="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 sales</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl1" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl1">Cost of Goods and Services Sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl1" />
    <link:loc xlink:type="locator" xlink:href="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 Sales</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl1">Cost of Goods and Service [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="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 Sales [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesMember_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl1">Cost of Sales [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl1" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl1" />
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    <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/label" xlink:title="us-gaap_CostsAndExpenses_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl1">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_lbl1" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CreditConcentrationRiskMember" xlink:label="CreditConcentrationRiskMember" xlink:title="CreditConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CreditConcentrationRiskMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CreditConcentrationRiskMember_lbl" xml:lang="en-US" id="us-gaap_CreditConcentrationRiskMember_lbl">Credit Concentration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CreditConcentrationRiskMember" xlink:to="us-gaap_CreditConcentrationRiskMember_lbl" xlink:title="label: CreditConcentrationRiskMember to us-gaap_CreditConcentrationRiskMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="CustomerConcentrationRiskMember" xlink:title="CustomerConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl">Strategic Partner [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember_lbl" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl1" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl1">Customer Concentration Risk [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="DisaggregationOfRevenueTable" xlink:title="DisaggregationOfRevenueTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueTable_lbl" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueTable_lbl">Disaggregation of Revenue [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DisaggregationOfRevenueTable" xlink:to="us-gaap_DisaggregationOfRevenueTable_lbl" xlink:title="label: DisaggregationOfRevenueTable to us-gaap_DisaggregationOfRevenueTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="DisaggregationOfRevenueLineItems" xlink:title="DisaggregationOfRevenueLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueLineItems_lbl" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueLineItems_lbl">Disaggregation of Revenue [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="us-gaap_DisaggregationOfRevenueLineItems_lbl" xlink:title="label: DisaggregationOfRevenueLineItems to us-gaap_DisaggregationOfRevenueLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtDisclosureAbstract" xlink:label="DebtDisclosureAbstract" xlink:title="DebtDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_DebtDisclosureAbstract_lbl">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureAbstract" xlink:to="us-gaap_DebtDisclosureAbstract_lbl" xlink:title="label: DebtDisclosureAbstract to us-gaap_DebtDisclosureAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:label="DebtInstrumentConvertibleConversionPrice1" xlink:title="DebtInstrumentConvertibleConversionPrice1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl">Conversion price per share (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPrice1" xlink:to="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" xlink:title="label: DebtInstrumentConvertibleConversionPrice1 to us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentRepurchasedFaceAmount" xlink:label="DebtInstrumentRepurchasedFaceAmount" xlink:title="DebtInstrumentRepurchasedFaceAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl">Principal amount repurchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentRepurchasedFaceAmount" xlink:to="us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl" xlink:title="label: DebtInstrumentRepurchasedFaceAmount to us-gaap_DebtInstrumentRepurchasedFaceAmount_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="DebtInstrumentFaceAmount" xlink:title="DebtInstrumentFaceAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_DebtInstrumentFaceAmount_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount_lbl">Face amount of offering</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount_lbl" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentFaceAmount_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount_lbl1">Debt Instrument, Face Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount_lbl1" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentTable" xlink:label="DebtInstrumentTable" xlink:title="DebtInstrumentTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentTable_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentTable_lbl">Schedule of Long-term Debt Instruments [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentTable" xlink:to="us-gaap_DebtInstrumentTable_lbl" xlink:title="label: DebtInstrumentTable to us-gaap_DebtInstrumentTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentAxis_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentAxis_lbl">Debt Instrument [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentAxis" xlink:to="us-gaap_DebtInstrumentAxis_lbl" xlink:title="label: DebtInstrumentAxis to us-gaap_DebtInstrumentAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="DebtInstrumentCarryingAmount" xlink:title="DebtInstrumentCarryingAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentCarryingAmount_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentCarryingAmount_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentCarryingAmount_lbl">Outstanding principal balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentCarryingAmount" xlink:to="us-gaap_DebtInstrumentCarryingAmount_lbl" xlink:title="label: DebtInstrumentCarryingAmount to us-gaap_DebtInstrumentCarryingAmount_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtDisclosureTextBlock" xlink:label="DebtDisclosureTextBlock" xlink:title="DebtDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_DebtDisclosureTextBlock_lbl">Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureTextBlock" xlink:to="us-gaap_DebtDisclosureTextBlock_lbl" xlink:title="label: DebtDisclosureTextBlock to us-gaap_DebtDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DebtDisclosureTextBlock_lbl1">Debt Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureTextBlock" xlink:to="us-gaap_DebtDisclosureTextBlock_lbl1" xlink:title="label: DebtDisclosureTextBlock to us-gaap_DebtDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="DebtInstrumentLineItems" xlink:title="DebtInstrumentLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentLineItems_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentLineItems_lbl">Debt Instrument [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentLineItems" xlink:to="us-gaap_DebtInstrumentLineItems_lbl" xlink:title="label: DebtInstrumentLineItems to us-gaap_DebtInstrumentLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentNameDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentNameDomain_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentNameDomain_lbl">Debt Instrument, Name [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNameDomain" xlink:to="us-gaap_DebtInstrumentNameDomain_lbl" xlink:title="label: DebtInstrumentNameDomain to us-gaap_DebtInstrumentNameDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl">Interest rate on convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateStatedPercentage" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl" xlink:title="label: DebtInstrumentInterestRateStatedPercentage to us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1">Interest rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateStatedPercentage" xlink:to="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" xlink:title="label: DebtInstrumentInterestRateStatedPercentage to us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="DebtInstrumentInterestRateEffectivePercentage" xlink:title="DebtInstrumentInterestRateEffectivePercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl">Effective interest rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateEffectivePercentage" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" xlink:title="label: DebtInstrumentInterestRateEffectivePercentage to us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1">Debt Instrument, Interest Rate, Effective Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateEffectivePercentage" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xlink:title="label: DebtInstrumentInterestRateEffectivePercentage to us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentMaturityDate" xlink:label="DebtInstrumentMaturityDate" xlink:title="DebtInstrumentMaturityDate" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentMaturityDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentMaturityDate_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentMaturityDate_lbl">Maturity date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentMaturityDate" xlink:to="us-gaap_DebtInstrumentMaturityDate_lbl" xlink:title="label: DebtInstrumentMaturityDate to us-gaap_DebtInstrumentMaturityDate_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_DeferredFinanceCostsNet" xlink:label="DeferredFinanceCostsNet" xlink:title="DeferredFinanceCostsNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredFinanceCostsNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DeferredFinanceCostsNet_lbl" xml:lang="en-US" id="us-gaap_DeferredFinanceCostsNet_lbl">Unamortized debt issuance costs</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredFinanceCostsNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DeferredFinanceCostsNet_lbl1" xml:lang="en-US" id="us-gaap_DeferredFinanceCostsNet_lbl1">Debt Issuance Costs, Net</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Depreciation" xlink:to="us-gaap_Depreciation_lbl" xlink:title="label: Depreciation to us-gaap_Depreciation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Depreciation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Depreciation_lbl1" xml:lang="en-US" id="us-gaap_Depreciation_lbl1">Depreciation</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_EarningsPerSharePolicyTextBlock" xlink:label="EarningsPerSharePolicyTextBlock" xlink:title="EarningsPerSharePolicyTextBlock" />
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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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel1Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueInputsLevel1Member_lbl1" xml:lang="en-US" id="us-gaap_FairValueInputsLevel1Member_lbl1">Fair Value, Inputs, Level 1 [Member]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherOperatingAssets" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xlink:title="label: IncreaseDecreaseInOtherOperatingAssets to us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:label="IncreaseDecreaseInOperatingCapitalAbstract" xlink:title="IncreaseDecreaseInOperatingCapitalAbstract" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInInventories_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_IncreaseDecreaseInInventories_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInInventories_lbl">Inventories</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInInventories_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInInventories_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInInventories_lbl1">Increase (Decrease) in Inventories</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInInventories" xlink:to="us-gaap_IncreaseDecreaseInInventories_lbl1" xlink:title="label: IncreaseDecreaseInInventories to us-gaap_IncreaseDecreaseInInventories_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:label="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl">Accrued compensation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1">Increase (Decrease) in Other Employee-Related Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:label="IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="IncreaseDecreaseInStockholdersEquityRollForward" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl">Increase (Decrease) in Stockholders' Equity [Roll Forward]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1">Increase (Decrease) in Stockholders' Equity [Roll Forward]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IntangibleAssetsFiniteLivedPolicy" xlink:label="IntangibleAssetsFiniteLivedPolicy" xlink:title="IntangibleAssetsFiniteLivedPolicy" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl" xml:lang="en-US" id="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl">Patent Expenses</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" xml:lang="en-US" id="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1">Intangible Assets, Finite-Lived, Policy [Policy Text Block]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestExpense_lbl1" xml:lang="en-US" id="us-gaap_InterestExpense_lbl1">Interest Expense</link:label>
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    <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" />
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    <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" />
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    <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" />
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    <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>
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    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl1">Investment, Policy [Policy Text Block]</link:label>
    <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" />
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    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl1">Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl1" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="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_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:label="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:title="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:to="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" xlink:title="label: LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract to us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1">Long-term Debt, by Type, Current and Noncurrent [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:to="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" xlink:title="label: LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract to us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="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_MinorityInterestPeriodIncreaseDecrease" xlink:label="MinorityInterestPeriodIncreaseDecrease" xlink:title="MinorityInterestPeriodIncreaseDecrease" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl">Noncontrolling interest in Akcea Therapeutics, Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestPeriodIncreaseDecrease" xlink:to="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" xlink:title="label: MinorityInterestPeriodIncreaseDecrease to us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xml:lang="en-US" id="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1">Noncontrolling Interest, Period Increase (Decrease)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestPeriodIncreaseDecrease" xlink:to="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xlink:title="label: MinorityInterestPeriodIncreaseDecrease to us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestLineItems_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestLineItems_lbl">Noncontrolling Interest [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestLineItems" xlink:to="us-gaap_MinorityInterestLineItems_lbl" xlink:title="label: MinorityInterestLineItems to us-gaap_MinorityInterestLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MinorityInterestOwnershipPercentageByParent" xlink:label="MinorityInterestOwnershipPercentageByParent" xlink:title="MinorityInterestOwnershipPercentageByParent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl">Percentage ownership</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestOwnershipPercentageByParent" xlink:to="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl" xlink:title="label: MinorityInterestOwnershipPercentageByParent to us-gaap_MinorityInterestOwnershipPercentageByParent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1" xml:lang="en-US" id="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1">Noncontrolling Interest, Ownership Percentage by Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestOwnershipPercentageByParent" xlink:to="us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1" xlink:title="label: MinorityInterestOwnershipPercentageByParent to us-gaap_MinorityInterestOwnershipPercentageByParent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestTable_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestTable_lbl">Noncontrolling Interest [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinorityInterestTable" xlink:to="us-gaap_MinorityInterestTable_lbl" xlink:title="label: MinorityInterestTable to us-gaap_MinorityInterestTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="NetCashProvidedByUsedInOperatingActivities" xlink:title="NetCashProvidedByUsedInOperatingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl">Net cash used in operating activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" xlink:title="label: NetCashProvidedByUsedInOperatingActivities to us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1">Net Cash Provided by (Used in) Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInOperatingActivities to us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetIncomeLoss_lbl" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl">Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetIncomeLoss_lbl1" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl1">Net loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl1" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_NetIncomeLoss_lbl2" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl2">Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl2" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl2" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetIncomeLoss_lbl3" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetIncomeLoss_lbl3" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl3">Net Income (Loss) Attributable to Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLoss" xlink:to="us-gaap_NetIncomeLoss_lbl3" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl3" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInInvestingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl">Investing activities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xlink:title="label: NetCashProvidedByUsedInInvestingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Investing Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInInvestingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl">Operating activities:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Operating Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInOperatingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="NetCashProvidedByUsedInInvestingActivities" xlink:title="NetCashProvidedByUsedInInvestingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl">Net cash provided by (used in) investing activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" xlink:title="label: NetCashProvidedByUsedInInvestingActivities to us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1">Net Cash Provided by (Used in) Investing Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInInvestingActivities to us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetIncomeLossAvailableToCommonStockholdersBasic" xlink:to="us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_lbl" xlink:title="label: NetIncomeLossAvailableToCommonStockholdersBasic to us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:to="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" xlink:title="label: NewAccountingPronouncementsPolicyPolicyTextBlock to us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" />
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    <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_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
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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_ProductMember" xlink:label="ProductMember" xlink:title="ProductMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProductMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProductMember_lbl" xml:lang="en-US" id="us-gaap_ProductMember_lbl">TEGSEDI and WAYLIVRA Revenue, Net [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductMember" xlink:to="us-gaap_ProductMember_lbl" xlink:title="label: ProductMember to us-gaap_ProductMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProductMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProductMember_lbl1" xml:lang="en-US" id="us-gaap_ProductMember_lbl1">Product [Member]</link:label>
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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_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProfitLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProfitLoss_lbl" xml:lang="en-US" id="us-gaap_ProfitLoss_lbl">Net 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_PropertyPlantAndEquipmentNet" xlink:label="PropertyPlantAndEquipmentNet" xlink:title="PropertyPlantAndEquipmentNet" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_PublicUtilitiesInventoryTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PublicUtilitiesInventoryTypeDomain_lbl" xml:lang="en-US" id="us-gaap_PublicUtilitiesInventoryTypeDomain_lbl">Inventory [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PublicUtilitiesInventoryTypeDomain" xlink:to="us-gaap_PublicUtilitiesInventoryTypeDomain_lbl" xlink:title="label: PublicUtilitiesInventoryTypeDomain to us-gaap_PublicUtilitiesInventoryTypeDomain_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringAndRelatedCostExpectedCost1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringAndRelatedCostExpectedCost1_lbl1" xml:lang="en-US" id="us-gaap_RestructuringAndRelatedCostExpectedCost1_lbl1">Restructuring and Related Cost, Expected Cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringAndRelatedCostExpectedCost1" xlink:to="us-gaap_RestructuringAndRelatedCostExpectedCost1_lbl1" xlink:title="label: RestructuringAndRelatedCostExpectedCost1 to us-gaap_RestructuringAndRelatedCostExpectedCost1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestructuringCharges" xlink:label="RestructuringCharges" xlink:title="RestructuringCharges" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringCharges_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_RestructuringCharges_lbl" xml:lang="en-US" id="us-gaap_RestructuringCharges_lbl">Amounts expensed during the period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringCharges" xlink:to="us-gaap_RestructuringCharges_lbl" xlink:title="label: RestructuringCharges to us-gaap_RestructuringCharges_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringCharges_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringCharges_lbl1" xml:lang="en-US" id="us-gaap_RestructuringCharges_lbl1">Restructuring Charges</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringCharges" xlink:to="us-gaap_RestructuringCharges_lbl1" xlink:title="label: RestructuringCharges to us-gaap_RestructuringCharges_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestructuringReserve" xlink:label="RestructuringReserve" xlink:title="RestructuringReserve" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringReserve_lbl" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_RestructuringReserve_lbl" xml:lang="en-US" id="us-gaap_RestructuringReserve_lbl">Beginning balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringReserve" xlink:to="us-gaap_RestructuringReserve_lbl" xlink:title="label: RestructuringReserve to us-gaap_RestructuringReserve_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringReserve_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_RestructuringReserve_lbl1" xml:lang="en-US" id="us-gaap_RestructuringReserve_lbl1">Ending balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringReserve" xlink:to="us-gaap_RestructuringReserve_lbl1" xlink:title="label: RestructuringReserve to us-gaap_RestructuringReserve_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringReserve_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringReserve_lbl2" xml:lang="en-US" id="us-gaap_RestructuringReserve_lbl2">Restructuring Reserve</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringReserve" xlink:to="us-gaap_RestructuringReserve_lbl2" xlink:title="label: RestructuringReserve to us-gaap_RestructuringReserve_lbl2" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestructuringCostAndReserveLineItems" xlink:label="RestructuringCostAndReserveLineItems" xlink:title="RestructuringCostAndReserveLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringCostAndReserveLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringCostAndReserveLineItems_lbl" xml:lang="en-US" id="us-gaap_RestructuringCostAndReserveLineItems_lbl">Restructuring Cost and Reserve [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringCostAndReserveLineItems" xlink:to="us-gaap_RestructuringCostAndReserveLineItems_lbl" xlink:title="label: RestructuringCostAndReserveLineItems to us-gaap_RestructuringCostAndReserveLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestructuringAndRelatedActivitiesAbstract" xlink:label="RestructuringAndRelatedActivitiesAbstract" xlink:title="RestructuringAndRelatedActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringAndRelatedActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringAndRelatedActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_RestructuringAndRelatedActivitiesAbstract_lbl">Severance and Retention Costs [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringAndRelatedActivitiesAbstract" xlink:to="us-gaap_RestructuringAndRelatedActivitiesAbstract_lbl" xlink:title="label: RestructuringAndRelatedActivitiesAbstract to us-gaap_RestructuringAndRelatedActivitiesAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestructuringReserveAccrualAdjustment1" xlink:label="RestructuringReserveAccrualAdjustment1" xlink:title="RestructuringReserveAccrualAdjustment1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringReserveAccrualAdjustment1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RestructuringReserveAccrualAdjustment1_lbl" xml:lang="en-US" id="us-gaap_RestructuringReserveAccrualAdjustment1_lbl">Reserve adjustments during the period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringReserveAccrualAdjustment1" xlink:to="us-gaap_RestructuringReserveAccrualAdjustment1_lbl" xlink:title="label: RestructuringReserveAccrualAdjustment1 to us-gaap_RestructuringReserveAccrualAdjustment1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringReserveAccrualAdjustment1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringReserveAccrualAdjustment1_lbl1" xml:lang="en-US" id="us-gaap_RestructuringReserveAccrualAdjustment1_lbl1">Restructuring Reserve, Accrual Adjustment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringReserveAccrualAdjustment1" xlink:to="us-gaap_RestructuringReserveAccrualAdjustment1_lbl1" xlink:title="label: RestructuringReserveAccrualAdjustment1 to us-gaap_RestructuringReserveAccrualAdjustment1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestructuringCostsAbstract" xlink:label="RestructuringCostsAbstract" xlink:title="RestructuringCostsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringCostsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RestructuringCostsAbstract_lbl" xml:lang="en-US" id="us-gaap_RestructuringCostsAbstract_lbl">Severance and Retention Costs [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringCostsAbstract" xlink:to="us-gaap_RestructuringCostsAbstract_lbl" xlink:title="label: RestructuringCostsAbstract to us-gaap_RestructuringCostsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringCostsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringCostsAbstract_lbl1" xml:lang="en-US" id="us-gaap_RestructuringCostsAbstract_lbl1">Restructuring Costs [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringCostsAbstract" xlink:to="us-gaap_RestructuringCostsAbstract_lbl1" xlink:title="label: RestructuringCostsAbstract to us-gaap_RestructuringCostsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestructuringCostAndReserveAxis" xlink:label="RestructuringCostAndReserveAxis" xlink:title="RestructuringCostAndReserveAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringCostAndReserveAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringCostAndReserveAxis_lbl" xml:lang="en-US" id="us-gaap_RestructuringCostAndReserveAxis_lbl">Restructuring Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringCostAndReserveAxis" xlink:to="us-gaap_RestructuringCostAndReserveAxis_lbl" xlink:title="label: RestructuringCostAndReserveAxis to us-gaap_RestructuringCostAndReserveAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1" xlink:label="RestructuringAndRelatedCostExpectedCostRemaining1" xlink:title="RestructuringAndRelatedCostExpectedCostRemaining1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl" xml:lang="en-US" id="us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl">Remaining estimated expenses to be recognized through October 2021</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringAndRelatedCostExpectedCostRemaining1" xlink:to="us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl" xlink:title="label: RestructuringAndRelatedCostExpectedCostRemaining1 to us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl1" xml:lang="en-US" id="us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl1">Restructuring and Related Cost, Expected Cost Remaining</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringAndRelatedCostExpectedCostRemaining1" xlink:to="us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl1" xlink:title="label: RestructuringAndRelatedCostExpectedCostRemaining1 to us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock" xlink:label="RestructuringAndRelatedActivitiesDisclosureTextBlock" xlink:title="RestructuringAndRelatedActivitiesDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl">Severance and Retention Costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringAndRelatedActivitiesDisclosureTextBlock" xlink:to="us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl" xlink:title="label: RestructuringAndRelatedActivitiesDisclosureTextBlock to us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl1">Restructuring and Related Activities Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringAndRelatedActivitiesDisclosureTextBlock" xlink:to="us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl1" xlink:title="label: RestructuringAndRelatedActivitiesDisclosureTextBlock to us-gaap_RestructuringAndRelatedActivitiesDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="RetainedEarningsAccumulatedDeficit" xlink:title="RetainedEarningsAccumulatedDeficit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RetainedEarningsAccumulatedDeficit_lbl" xml:lang="en-US" id="us-gaap_RetainedEarningsAccumulatedDeficit_lbl">Accumulated deficit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsAccumulatedDeficit" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_lbl" xlink:title="label: RetainedEarningsAccumulatedDeficit to us-gaap_RetainedEarningsAccumulatedDeficit_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" xml:lang="en-US" id="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1">Retained Earnings (Accumulated Deficit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsAccumulatedDeficit" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" xlink:title="label: RetainedEarningsAccumulatedDeficit to us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RetainedEarningsMember" xlink:label="RetainedEarningsMember" xlink:title="RetainedEarningsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RetainedEarningsMember_lbl" xml:lang="en-US" id="us-gaap_RetainedEarningsMember_lbl">Accumulated Deficit [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsMember" xlink:to="us-gaap_RetainedEarningsMember_lbl" xlink:title="label: RetainedEarningsMember to us-gaap_RetainedEarningsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RetainedEarningsMember_lbl1" xml:lang="en-US" id="us-gaap_RetainedEarningsMember_lbl1">Retained Earnings [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsMember" xlink:to="us-gaap_RetainedEarningsMember_lbl1" xlink:title="label: RetainedEarningsMember to us-gaap_RetainedEarningsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerMember" xlink:label="RevenueFromContractWithCustomerMember" xlink:title="RevenueFromContractWithCustomerMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerMember_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerMember_lbl">Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerMember" xlink:to="us-gaap_RevenueFromContractWithCustomerMember_lbl" xlink:title="label: RevenueFromContractWithCustomerMember to us-gaap_RevenueFromContractWithCustomerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerMember_lbl1">Revenue from Contract with Customer Benchmark [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerMember" xlink:to="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xlink:title="label: RevenueFromContractWithCustomerMember to us-gaap_RevenueFromContractWithCustomerMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerAbstract" xlink:label="RevenueFromContractWithCustomerAbstract" xlink:title="RevenueFromContractWithCustomerAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract_lbl">Revenue Recognition [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xlink:title="label: RevenueFromContractWithCustomerAbstract to us-gaap_RevenueFromContractWithCustomerAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1">Revenue from Contract with Customer [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xlink:title="label: RevenueFromContractWithCustomerAbstract to us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RevenueFromContractWithCustomerPolicyTextBlock" xlink:label="RevenueFromContractWithCustomerPolicyTextBlock" xlink:title="RevenueFromContractWithCustomerPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl">Revenue Recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerPolicyTextBlock" xlink:to="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl" xlink:title="label: RevenueFromContractWithCustomerPolicyTextBlock to us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1">Revenue from Contract with Customer [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerPolicyTextBlock" xlink:to="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1" xlink:title="label: RevenueFromContractWithCustomerPolicyTextBlock to us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate</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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Risk Free Interest Rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:title="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_lbl" xlink:title="label: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl">Stock-Based Compensation Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:to="us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl" xlink:title="label: ShareBasedCompensationOptionAndIncentivePlansPolicy to us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl1">Share-based Payment Arrangement [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:to="us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl1" xlink:title="label: ShareBasedCompensationOptionAndIncentivePlansPolicy to us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy_lbl1" />
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    <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" />
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    <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" />
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    <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" />
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    <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" />
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    <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_SignificantAccountingPoliciesTextBlock" xlink:label="SignificantAccountingPoliciesTextBlock" xlink:title="SignificantAccountingPoliciesTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SignificantAccountingPoliciesTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SignificantAccountingPoliciesTextBlock_lbl" xml:lang="en-US" id="us-gaap_SignificantAccountingPoliciesTextBlock_lbl">Significant Accounting Policies</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantAccountingPoliciesTextBlock" xlink:to="us-gaap_SignificantAccountingPoliciesTextBlock_lbl" xlink:title="label: SignificantAccountingPoliciesTextBlock to us-gaap_SignificantAccountingPoliciesTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1">Significant Accounting Policies [Text Block]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfFinancialPositionAbstract" xlink:to="us-gaap_StatementOfFinancialPositionAbstract_lbl1" xlink:title="label: StatementOfFinancialPositionAbstract to us-gaap_StatementOfFinancialPositionAbstract_lbl1" />
    <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" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedAndRetiredDuringPeriodShares" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" xlink:title="label: StockRepurchasedAndRetiredDuringPeriodShares to us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" />
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    <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" />
    <link:label xlink:type="resource" xlink:label="srt_ProductsAndServicesDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductsAndServicesDomain_lbl" xml:lang="en-US" id="srt_ProductsAndServicesDomain_lbl">Products and Services [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductsAndServicesDomain" xlink:to="srt_ProductsAndServicesDomain_lbl" xlink:title="label: ProductsAndServicesDomain to srt_ProductsAndServicesDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ProductOrServiceAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductOrServiceAxis_lbl" xml:lang="en-US" id="srt_ProductOrServiceAxis_lbl">Products and Services [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductOrServiceAxis" xlink:to="srt_ProductOrServiceAxis_lbl" xlink:title="label: ProductOrServiceAxis to srt_ProductOrServiceAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember" xlink:label="RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember" xlink:title="RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember" />
    <link:label xlink:type="resource" xlink:label="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl" xml:lang="en-US" id="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl">Adjustment [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember" xlink:to="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl" xlink:title="label: RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember to srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl1" xml:lang="en-US" id="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl1">Revision of Prior Period, Accounting Standards Update, Adjustment [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember" xlink:to="srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl1" xlink:title="label: RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember to srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:label xlink:type="resource" xlink:label="srt_RangeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeAxis_lbl" xml:lang="en-US" id="srt_RangeAxis_lbl">Statistical Measurement [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeAxis" xlink:to="srt_RangeAxis_lbl" xlink:title="label: RangeAxis to srt_RangeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:label xlink:type="resource" xlink:label="srt_RangeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeMember_lbl" xml:lang="en-US" id="srt_RangeMember_lbl">Statistical Measurement [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeMember" xlink:to="srt_RangeMember_lbl" xlink:title="label: RangeMember to srt_RangeMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RestatementDomain" xlink:label="RestatementDomain" xlink:title="RestatementDomain" />
    <link:label xlink:type="resource" xlink:label="srt_RestatementDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RestatementDomain_lbl" xml:lang="en-US" id="srt_RestatementDomain_lbl">Revision of Prior Period [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestatementDomain" xlink:to="srt_RestatementDomain_lbl" xlink:title="label: RestatementDomain to srt_RestatementDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_RestatementAxis" xlink:label="RestatementAxis" xlink:title="RestatementAxis" />
    <link:label xlink:type="resource" xlink:label="srt_RestatementAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RestatementAxis_lbl" xml:lang="en-US" id="srt_RestatementAxis_lbl">Revision of Prior Period [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestatementAxis" xlink:to="srt_RestatementAxis_lbl" xlink:title="label: RestatementAxis to srt_RestatementAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ScenarioPreviouslyReportedMember" xlink:label="ScenarioPreviouslyReportedMember" xlink:title="ScenarioPreviouslyReportedMember" />
    <link:label xlink:type="resource" xlink:label="srt_ScenarioPreviouslyReportedMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="srt_ScenarioPreviouslyReportedMember_lbl" xml:lang="en-US" id="srt_ScenarioPreviouslyReportedMember_lbl">As Previously Reported [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScenarioPreviouslyReportedMember" xlink:to="srt_ScenarioPreviouslyReportedMember_lbl" xlink:title="label: ScenarioPreviouslyReportedMember to srt_ScenarioPreviouslyReportedMember_lbl" />
    <link:label xlink:type="resource" xlink:label="srt_ScenarioPreviouslyReportedMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ScenarioPreviouslyReportedMember_lbl1" xml:lang="en-US" id="srt_ScenarioPreviouslyReportedMember_lbl1">Previously Reported [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScenarioPreviouslyReportedMember" xlink:to="srt_ScenarioPreviouslyReportedMember_lbl1" xlink:title="label: ScenarioPreviouslyReportedMember to srt_ScenarioPreviouslyReportedMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ScenarioUnspecifiedDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ScenarioUnspecifiedDomain_lbl" xml:lang="en-US" id="srt_ScenarioUnspecifiedDomain_lbl">Scenario [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScenarioUnspecifiedDomain" xlink:to="srt_ScenarioUnspecifiedDomain_lbl" xlink:title="label: ScenarioUnspecifiedDomain to srt_ScenarioUnspecifiedDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/srt/2020/elts/srt-2020-01-31.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:label xlink:type="resource" xlink:label="srt_StatementScenarioAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_StatementScenarioAxis_lbl" xml:lang="en-US" id="srt_StatementScenarioAxis_lbl">Scenario [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementScenarioAxis" xlink:to="srt_StatementScenarioAxis_lbl" xlink:title="label: StatementScenarioAxis to srt_StatementScenarioAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_CoverAbstract" xlink:label="CoverAbstract" xlink:title="CoverAbstract" />
    <link:label xlink:type="resource" xlink:label="dei_CoverAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CoverAbstract_lbl" xml:lang="en-US" id="dei_CoverAbstract_lbl">Cover [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CoverAbstract" xlink:to="dei_CoverAbstract_lbl" xlink:title="label: CoverAbstract to dei_CoverAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_EntityAddressAddressLine1" xlink:label="EntityAddressAddressLine1" xlink:title="EntityAddressAddressLine1" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressAddressLine1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressAddressLine1_lbl" xml:lang="en-US" id="dei_EntityAddressAddressLine1_lbl">Entity Address, Address Line One</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressAddressLine1" xlink:to="dei_EntityAddressAddressLine1_lbl" xlink:title="label: EntityAddressAddressLine1 to dei_EntityAddressAddressLine1_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_AmendmentFlag" xlink:label="AmendmentFlag" xlink:title="AmendmentFlag" />
    <link:label xlink:type="resource" xlink:label="dei_AmendmentFlag_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AmendmentFlag_lbl" xml:lang="en-US" id="dei_AmendmentFlag_lbl">Amendment Flag</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmendmentFlag" xlink:to="dei_AmendmentFlag_lbl" xlink:title="label: AmendmentFlag to dei_AmendmentFlag_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_CityAreaCode" xlink:label="CityAreaCode" xlink:title="CityAreaCode" />
    <link:label xlink:type="resource" xlink:label="dei_CityAreaCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CityAreaCode_lbl" xml:lang="en-US" id="dei_CityAreaCode_lbl">City Area Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CityAreaCode" xlink:to="dei_CityAreaCode_lbl" xlink:title="label: CityAreaCode to dei_CityAreaCode_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/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_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_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" />
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    <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>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2019/dei-2019-01-31.xsd#dei_DocumentQuarterlyReport" xlink:label="DocumentQuarterlyReport" xlink:title="DocumentQuarterlyReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentQuarterlyReport_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentQuarterlyReport_lbl" xml:lang="en-US" id="dei_DocumentQuarterlyReport_lbl">Document Quarterly Report</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_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-20210331.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-20210331.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>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl">0.125 percent convertible senior notes due December 2024.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl1">Convertible Senior Notes 0.125 Percent [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl2">0.125 Percent Convertible Senior Notes [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl">1 percent convertible senior notes due November 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl1">Convertible Senior Notes 1 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl2">1 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl3">1% Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_AroBiotherapeuticsMember" xlink:label="AroBiotherapeuticsMember" xlink:title="AroBiotherapeuticsMember" />
    <link:label xlink:type="resource" xlink:label="ions_AroBiotherapeuticsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AroBiotherapeuticsMember_lbl" xml:lang="en-US" id="ions_AroBiotherapeuticsMember_lbl">Aro Biotherapeutics is a biotechnology company pioneering the development of tissue-targeted genetic medicines with a platform based on a proprietary protein technology called Centyrins.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AroBiotherapeuticsMember" xlink:to="ions_AroBiotherapeuticsMember_lbl" xlink:title="label: AroBiotherapeuticsMember to ions_AroBiotherapeuticsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AroBiotherapeuticsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AroBiotherapeuticsMember_lbl1" xml:lang="en-US" id="ions_AroBiotherapeuticsMember_lbl1">Aro Biotherapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AroBiotherapeuticsMember" xlink:to="ions_AroBiotherapeuticsMember_lbl1" xlink:title="label: AroBiotherapeuticsMember to ions_AroBiotherapeuticsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AroBiotherapeuticsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AroBiotherapeuticsMember_lbl2" xml:lang="en-US" id="ions_AroBiotherapeuticsMember_lbl2">Aro Biotherapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AroBiotherapeuticsMember" xlink:to="ions_AroBiotherapeuticsMember_lbl2" xlink:title="label: AroBiotherapeuticsMember to ions_AroBiotherapeuticsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xml:lang="en-US" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl">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.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_DynacureSasMember" xlink:label="DynacureSasMember" xlink:title="DynacureSasMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_SuzhouRiboLifeScienceCoLtdMember" xlink:label="SuzhouRiboLifeScienceCoLtdMember" xlink:title="SuzhouRiboLifeScienceCoLtdMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" />
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2">After two years but within three and a half years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_MaximumContractMaturityPeriodRange1" xlink:label="MaximumContractMaturityPeriodRange1" xlink:title="MaximumContractMaturityPeriodRange1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl">The maximum contract maturity period for the first range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link: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>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_MaximumContractMaturityPeriodRange2" xlink:label="MaximumContractMaturityPeriodRange2" xlink:title="MaximumContractMaturityPeriodRange2" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl">The maximum contract maturity period for the second range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl1">Maximum contract maturity period, range 2</link:label>
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    <link: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-20210331.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>
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    <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-20210331.xsd#ions_ResearchDevelopmentAndPatentExpenseMember" xlink:label="ResearchDevelopmentAndPatentExpenseMember" xlink:title="ResearchDevelopmentAndPatentExpenseMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpenseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentExpenseMember_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpenseMember_lbl">Primary financial statement caption encompassing research, development and patent expenses.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:label="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:title="ShareBasedPaymentArrangementBoardOfDirectorMember" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl">Recipient, of award granted under share-based payment arrangement, over whom grantor exercises or has right to exercise sufficient control to establish employer-employee relationship based on law of pertinent jurisdiction. Includes nonemployee director treated as employee when acting as member of board of directors, if elected by grantor's shareholders or appointed to board position to be filled by shareholder election when existing term expires.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorMember to ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1">Share-based Payment Arrangement, Board of Director [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl">Number of separate performance periods under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Number of Performance Periods</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2">Number of performance periods</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl">Number of units guaranteed to vest under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl">Percentage of units guaranteed to vest under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" />
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.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-20210331.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-20210331.xsd#ions_SpinrazaRoyaltiesMember" xlink:label="SpinrazaRoyaltiesMember" xlink:title="SpinrazaRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SpinrazaRoyaltiesMember_lbl" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl">Royalty revenues from the sale of SPINRAZA (nusinersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SpinrazaRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl1">Spinraza Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl1" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SpinrazaRoyaltiesMember_lbl2" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl2">SPINRAZA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl2" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_LicensingAndOtherRoyaltiesMember" xlink:label="LicensingAndOtherRoyaltiesMember" xlink:title="LicensingAndOtherRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl">Revenue from license fees and other royalties, excluding royalties from the sale of SPINRAZA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl1">Licensing and Other Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl1" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl2" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl2">Licensing and Other Royalty Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl2" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.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/terseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2">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_lbl2" xlink:title="label: ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember to ions_ResearchAndDevelopmentRevenueUnderCollaborativeAgreementsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.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-20210331.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1">Collaborative Arrangements and Licensing Agreements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsAbstract to ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_SecuritiesWithMaturityOfOneYearOrLessMember" xlink:label="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:title="SecuritiesWithMaturityOfOneYearOrLessMember" />
    <link:label xlink:type="resource" xlink:label="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl" xml:lang="en-US" id="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl">Represents investment securities with an expected maturity of one year or less.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:to="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl" xlink:title="label: SecuritiesWithMaturityOfOneYearOrLessMember to ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1" xml:lang="en-US" id="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1">Securities with Maturity of One Year or Less [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:to="ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1" xlink:title="label: SecuritiesWithMaturityOfOneYearOrLessMember to ions_SecuritiesWithMaturityOfOneYearOrLessMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:label="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:title="SecuritiesWithMaturityOfMoreThanOneYearMember" />
    <link:label xlink:type="resource" xlink:label="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl" xml:lang="en-US" id="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl">Represents investment securities with an expected maturity of more than one year.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:to="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl" xlink:title="label: SecuritiesWithMaturityOfMoreThanOneYearMember to ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1" xml:lang="en-US" id="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1">Securities with Maturity of More than One Year [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:to="ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1" xlink:title="label: SecuritiesWithMaturityOfMoreThanOneYearMember to ions_SecuritiesWithMaturityOfMoreThanOneYearMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl">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).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl1">Debt Securities, Available-for-sale and Equity Securities, FV-NI, Cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl2" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl2">Cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl2">Estimated fair value</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_NumberOfAgreementsWithCollaborationPartner" xlink:label="NumberOfAgreementsWithCollaborationPartner" xlink:title="NumberOfAgreementsWithCollaborationPartner" />
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_UpfrontPaymentReceived" xlink:label="UpfrontPaymentReceived" xlink:title="UpfrontPaymentReceived" />
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.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>
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_Ion464Member" xlink:label="Ion464Member" xlink:title="Ion464Member" />
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    <link:loc xlink:type="locator" xlink:href="ions-20210331.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:loc xlink:type="locator" xlink:href="ions-20210331.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-20210331.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-20210331.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-20210331.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-20210331.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/verboseLabel" 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:loc xlink:type="locator" xlink:href="ions-20210331.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-20210331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember to ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl1">Collaborative Arrangement and Licensing Agreement Amended in February 2017 with Bayer [Member]</link:label>
    <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" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember_lbl2">Bayer [Member]</link:label>
    <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-20210331.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-20210331.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-20210331.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-20210331.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:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaTherapeuticsIncMember_lbl" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl">Akcea Therapeutics, Inc. is a subsidiary of the Company and was formed to develop and commercialize drugs for cardiometabolic disorders.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaTherapeuticsIncMember_lbl1" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl1">Akcea Therapeutics, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl1" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaTherapeuticsIncMember_lbl2" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl2">Akcea [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl2" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.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-20210331.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-20210331.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-20210331.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-20210331.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-20210331.xsd#ions_MilestonePaymentAchieved" xlink:label="MilestonePaymentAchieved" xlink:title="MilestonePaymentAchieved" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentAchieved_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MilestonePaymentAchieved_lbl" xml:lang="en-US" id="ions_MilestonePaymentAchieved_lbl">Milestone payment achieved during the period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentAchieved" xlink:to="ions_MilestonePaymentAchieved_lbl" xlink:title="label: MilestonePaymentAchieved to ions_MilestonePaymentAchieved_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentAchieved_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MilestonePaymentAchieved_lbl1" xml:lang="en-US" id="ions_MilestonePaymentAchieved_lbl1">Milestone payment achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentAchieved" xlink:to="ions_MilestonePaymentAchieved_lbl1" xlink:title="label: MilestonePaymentAchieved to ions_MilestonePaymentAchieved_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.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-20210331.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-20210331.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-20210331.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-20210331.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-20210331.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-20210331.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl">Disclosure of information about collaborative arrangements and non-collaborative arrangement transactions.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl">Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2">Collaborative Arrangements and Licensing Agreements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.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-20210331.xsd#ions_PeriodAfterBillingWhenPaymentIsReceived" xlink:label="PeriodAfterBillingWhenPaymentIsReceived" xlink:title="PeriodAfterBillingWhenPaymentIsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl">The time period between billing a collaboration partner for goods delivered or services performed that are due unconditionally and payment is received from the collaboration partner, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1">Period after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2">Period of time after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_SignificantPartnersAbstract" xlink:label="SignificantPartnersAbstract" xlink:title="SignificantPartnersAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_SignificantPartnersAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SignificantPartnersAbstract_lbl1" xml:lang="en-US" id="ions_SignificantPartnersAbstract_lbl1">Significant Partners [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantPartnersAbstract" xlink:to="ions_SignificantPartnersAbstract_lbl1" xlink:title="label: SignificantPartnersAbstract to ions_SignificantPartnersAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_NumberOfSignificantCustomers" xlink:label="NumberOfSignificantCustomers" xlink:title="NumberOfSignificantCustomers" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfSignificantCustomers_lbl" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl">The number of significant customers with which the Company does business.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfSignificantCustomers_lbl1" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl1">Number of Significant Customers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl1" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfSignificantCustomers_lbl2" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl2">Number of significant customers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl2" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_TwoSignificantCustomersMember" xlink:label="TwoSignificantCustomersMember" xlink:title="TwoSignificantCustomersMember" />
    <link:label xlink:type="resource" xlink:label="ions_TwoSignificantCustomersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TwoSignificantCustomersMember_lbl" xml:lang="en-US" id="ions_TwoSignificantCustomersMember_lbl">Two significant corporate partners and leading global pharmaceutical companies that are working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under collaborative arrangement and licensing agreements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TwoSignificantCustomersMember" xlink:to="ions_TwoSignificantCustomersMember_lbl" xlink:title="label: TwoSignificantCustomersMember to ions_TwoSignificantCustomersMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TwoSignificantCustomersMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TwoSignificantCustomersMember_lbl1" xml:lang="en-US" id="ions_TwoSignificantCustomersMember_lbl1">Two Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TwoSignificantCustomersMember" xlink:to="ions_TwoSignificantCustomersMember_lbl1" xlink:title="label: TwoSignificantCustomersMember to ions_TwoSignificantCustomersMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TwoSignificantCustomersMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TwoSignificantCustomersMember_lbl2" xml:lang="en-US" id="ions_TwoSignificantCustomersMember_lbl2">Two Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TwoSignificantCustomersMember" xlink:to="ions_TwoSignificantCustomersMember_lbl2" xlink:title="label: TwoSignificantCustomersMember to ions_TwoSignificantCustomersMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_ThreeSignificantCustomersMember" xlink:label="ThreeSignificantCustomersMember" xlink:title="ThreeSignificantCustomersMember" />
    <link:label xlink:type="resource" xlink:label="ions_ThreeSignificantCustomersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ThreeSignificantCustomersMember_lbl" xml:lang="en-US" id="ions_ThreeSignificantCustomersMember_lbl">Three 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="ThreeSignificantCustomersMember" xlink:to="ions_ThreeSignificantCustomersMember_lbl" xlink:title="label: ThreeSignificantCustomersMember to ions_ThreeSignificantCustomersMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ThreeSignificantCustomersMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ThreeSignificantCustomersMember_lbl1" xml:lang="en-US" id="ions_ThreeSignificantCustomersMember_lbl1">Three Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ThreeSignificantCustomersMember" xlink:to="ions_ThreeSignificantCustomersMember_lbl1" xlink:title="label: ThreeSignificantCustomersMember to ions_ThreeSignificantCustomersMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ThreeSignificantCustomersMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ThreeSignificantCustomersMember_lbl2" xml:lang="en-US" id="ions_ThreeSignificantCustomersMember_lbl2">Three Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ThreeSignificantCustomersMember" xlink:to="ions_ThreeSignificantCustomersMember_lbl2" xlink:title="label: ThreeSignificantCustomersMember to ions_ThreeSignificantCustomersMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_DebtInstrumentNumberOfConvertibleNotes" xlink:label="DebtInstrumentNumberOfConvertibleNotes" xlink:title="DebtInstrumentNumberOfConvertibleNotes" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentNumberOfConvertibleNotes_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentNumberOfConvertibleNotes_lbl" xml:lang="en-US" id="ions_DebtInstrumentNumberOfConvertibleNotes_lbl">Number of outstanding convertible notes.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNumberOfConvertibleNotes" xlink:to="ions_DebtInstrumentNumberOfConvertibleNotes_lbl" xlink:title="label: DebtInstrumentNumberOfConvertibleNotes to ions_DebtInstrumentNumberOfConvertibleNotes_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" xml:lang="en-US" id="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1">Debt Instrument, Number of convertible notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNumberOfConvertibleNotes" xlink:to="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" xlink:title="label: DebtInstrumentNumberOfConvertibleNotes to ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentNumberOfConvertibleNotes_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentNumberOfConvertibleNotes_lbl2" xml:lang="en-US" id="ions_DebtInstrumentNumberOfConvertibleNotes_lbl2">Number of outstanding convertible notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNumberOfConvertibleNotes" xlink:to="ions_DebtInstrumentNumberOfConvertibleNotes_lbl2" xlink:title="label: DebtInstrumentNumberOfConvertibleNotes to ions_DebtInstrumentNumberOfConvertibleNotes_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_AccountingStandardsUpdate202006Member" xlink:label="AccountingStandardsUpdate202006Member" xlink:title="AccountingStandardsUpdate202006Member" />
    <link:label xlink:type="resource" xlink:label="ions_AccountingStandardsUpdate202006Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccountingStandardsUpdate202006Member_lbl" xml:lang="en-US" id="ions_AccountingStandardsUpdate202006Member_lbl">Accounting Standards Update 2020-06 Debt - Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and Hedging - Contracts in Entity's Own Equity (Subtopic 815-40): Accounting for Convertible Instruments and Contracts in an Entity's Own Equity.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountingStandardsUpdate202006Member" xlink:to="ions_AccountingStandardsUpdate202006Member_lbl" xlink:title="label: AccountingStandardsUpdate202006Member to ions_AccountingStandardsUpdate202006Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccountingStandardsUpdate202006Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccountingStandardsUpdate202006Member_lbl1" xml:lang="en-US" id="ions_AccountingStandardsUpdate202006Member_lbl1">Accounting Standards Update 2020-06 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountingStandardsUpdate202006Member" xlink:to="ions_AccountingStandardsUpdate202006Member_lbl1" xlink:title="label: AccountingStandardsUpdate202006Member to ions_AccountingStandardsUpdate202006Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccountingStandardsUpdate202006Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccountingStandardsUpdate202006Member_lbl2" xml:lang="en-US" id="ions_AccountingStandardsUpdate202006Member_lbl2">ASU 2020-06 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountingStandardsUpdate202006Member" xlink:to="ions_AccountingStandardsUpdate202006Member_lbl2" xlink:title="label: AccountingStandardsUpdate202006Member to ions_AccountingStandardsUpdate202006Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_SeveranceAndRetentionCostsTable" xlink:label="SeveranceAndRetentionCostsTable" xlink:title="SeveranceAndRetentionCostsTable" />
    <link:label xlink:type="resource" xlink:label="ions_SeveranceAndRetentionCostsTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SeveranceAndRetentionCostsTable_lbl" xml:lang="en-US" id="ions_SeveranceAndRetentionCostsTable_lbl">Disclosure of information about severance and retention costs.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SeveranceAndRetentionCostsTable" xlink:to="ions_SeveranceAndRetentionCostsTable_lbl" xlink:title="label: SeveranceAndRetentionCostsTable to ions_SeveranceAndRetentionCostsTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SeveranceAndRetentionCostsTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SeveranceAndRetentionCostsTable_lbl1" xml:lang="en-US" id="ions_SeveranceAndRetentionCostsTable_lbl1">Severance and Retention Costs [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SeveranceAndRetentionCostsTable" xlink:to="ions_SeveranceAndRetentionCostsTable_lbl1" xlink:title="label: SeveranceAndRetentionCostsTable to ions_SeveranceAndRetentionCostsTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_SeveranceAndRetentionCostsLineItems" xlink:label="SeveranceAndRetentionCostsLineItems" xlink:title="SeveranceAndRetentionCostsLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_SeveranceAndRetentionCostsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SeveranceAndRetentionCostsLineItems_lbl" xml:lang="en-US" id="ions_SeveranceAndRetentionCostsLineItems_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="SeveranceAndRetentionCostsLineItems" xlink:to="ions_SeveranceAndRetentionCostsLineItems_lbl" xlink:title="label: SeveranceAndRetentionCostsLineItems to ions_SeveranceAndRetentionCostsLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SeveranceAndRetentionCostsLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SeveranceAndRetentionCostsLineItems_lbl1" xml:lang="en-US" id="ions_SeveranceAndRetentionCostsLineItems_lbl1">Severance and Retention Costs [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SeveranceAndRetentionCostsLineItems" xlink:to="ions_SeveranceAndRetentionCostsLineItems_lbl1" xlink:title="label: SeveranceAndRetentionCostsLineItems to ions_SeveranceAndRetentionCostsLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SeveranceAndRetentionCostsLineItems_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SeveranceAndRetentionCostsLineItems_lbl2" xml:lang="en-US" id="ions_SeveranceAndRetentionCostsLineItems_lbl2">Severance and Retention Costs [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SeveranceAndRetentionCostsLineItems" xlink:to="ions_SeveranceAndRetentionCostsLineItems_lbl2" xlink:title="label: SeveranceAndRetentionCostsLineItems to ions_SeveranceAndRetentionCostsLineItems_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_RestructuredEuropeanOperationsMember" xlink:label="RestructuredEuropeanOperationsMember" xlink:title="RestructuredEuropeanOperationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_RestructuredEuropeanOperationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RestructuredEuropeanOperationsMember_lbl" xml:lang="en-US" id="ions_RestructuredEuropeanOperationsMember_lbl">Termination of employees and retention of key employees for a specific period of time associated with the restructuring of the Company's European operations.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuredEuropeanOperationsMember" xlink:to="ions_RestructuredEuropeanOperationsMember_lbl" xlink:title="label: RestructuredEuropeanOperationsMember to ions_RestructuredEuropeanOperationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RestructuredEuropeanOperationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RestructuredEuropeanOperationsMember_lbl1" xml:lang="en-US" id="ions_RestructuredEuropeanOperationsMember_lbl1">Restructured European Operations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuredEuropeanOperationsMember" xlink:to="ions_RestructuredEuropeanOperationsMember_lbl1" xlink:title="label: RestructuredEuropeanOperationsMember to ions_RestructuredEuropeanOperationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RestructuredEuropeanOperationsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RestructuredEuropeanOperationsMember_lbl2" xml:lang="en-US" id="ions_RestructuredEuropeanOperationsMember_lbl2">Restructured European Operations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuredEuropeanOperationsMember" xlink:to="ions_RestructuredEuropeanOperationsMember_lbl2" xlink:title="label: RestructuredEuropeanOperationsMember to ions_RestructuredEuropeanOperationsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_AkceaAcquisitionMember" xlink:label="AkceaAcquisitionMember" xlink:title="AkceaAcquisitionMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaAcquisitionMember_lbl" xml:lang="en-US" id="ions_AkceaAcquisitionMember_lbl">Termination of employees and retention of key employees for a specific period of time associated with the Akcea Acquisition.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionMember" xlink:to="ions_AkceaAcquisitionMember_lbl" xlink:title="label: AkceaAcquisitionMember to ions_AkceaAcquisitionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaAcquisitionMember_lbl1" xml:lang="en-US" id="ions_AkceaAcquisitionMember_lbl1">Akcea Acquisition [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionMember" xlink:to="ions_AkceaAcquisitionMember_lbl1" xlink:title="label: AkceaAcquisitionMember to ions_AkceaAcquisitionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaAcquisitionMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaAcquisitionMember_lbl2" xml:lang="en-US" id="ions_AkceaAcquisitionMember_lbl2">Akcea Acquisition [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaAcquisitionMember" xlink:to="ions_AkceaAcquisitionMember_lbl2" xlink:title="label: AkceaAcquisitionMember to ions_AkceaAcquisitionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.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-20210331.xsd#ions_RestructuringReserveNetExpense" xlink:label="RestructuringReserveNetExpense" xlink:title="RestructuringReserveNetExpense" />
    <link:label xlink:type="resource" xlink:label="ions_RestructuringReserveNetExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RestructuringReserveNetExpense_lbl" xml:lang="en-US" id="ions_RestructuringReserveNetExpense_lbl">Amount of expenses associated with exit or disposal activities pursuant to an authorized plan, net of adjustments to a previously accrued restructuring liability. The net expense increases (decreases) the accrual for restructuring costs.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringReserveNetExpense" xlink:to="ions_RestructuringReserveNetExpense_lbl" xlink:title="label: RestructuringReserveNetExpense to ions_RestructuringReserveNetExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RestructuringReserveNetExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RestructuringReserveNetExpense_lbl1" xml:lang="en-US" id="ions_RestructuringReserveNetExpense_lbl1">Restructuring Reserve, Net Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringReserveNetExpense" xlink:to="ions_RestructuringReserveNetExpense_lbl1" xlink:title="label: RestructuringReserveNetExpense to ions_RestructuringReserveNetExpense_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RestructuringReserveNetExpense_lbl2" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_RestructuringReserveNetExpense_lbl2" xml:lang="en-US" id="ions_RestructuringReserveNetExpense_lbl2">Net amount expensed during the period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuringReserveNetExpense" xlink:to="ions_RestructuringReserveNetExpense_lbl2" xlink:title="label: RestructuringReserveNetExpense to ions_RestructuringReserveNetExpense_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_RestructuredNorthAmericanTEGSEDIOperationsMember" xlink:label="RestructuredNorthAmericanTEGSEDIOperationsMember" xlink:title="RestructuredNorthAmericanTEGSEDIOperationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl" xml:lang="en-US" id="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl">Restructuring of the Akcea workforce in the Company's North American TEGSEDI Operations.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuredNorthAmericanTEGSEDIOperationsMember" xlink:to="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl" xlink:title="label: RestructuredNorthAmericanTEGSEDIOperationsMember to ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl1" xml:lang="en-US" id="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl1">Restructured North American TEGSEDI Operations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuredNorthAmericanTEGSEDIOperationsMember" xlink:to="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl1" xlink:title="label: RestructuredNorthAmericanTEGSEDIOperationsMember to ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl2" xml:lang="en-US" id="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl2">Restructured North American TEGSEDI Operations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestructuredNorthAmericanTEGSEDIOperationsMember" xlink:to="ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl2" xlink:title="label: RestructuredNorthAmericanTEGSEDIOperationsMember to ions_RestructuredNorthAmericanTEGSEDIOperationsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20210331.xsd#ions_ConvertibleNotesDisclosureTable" xlink:label="ConvertibleNotesDisclosureTable" xlink:title="ConvertibleNotesDisclosureTable" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleNotesDisclosureTable_lbl" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureTable_lbl">Disclosure of information about income taxes.</link:label>
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</TEXT>
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<DOCUMENT>
<TYPE>EX-101.PRE
<SEQUENCE>11
<FILENAME>ions-20210331_pre.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
<TEXT>
<XBRL>
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1.&#160; 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;We prepared the unaudited interim condensed consolidated financial statements for the &lt;/span&gt;three months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;March 31, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on the same basis as the audited financial statements for the year ended &lt;/span&gt;December 31, 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, with the exception of our retrospective adoption of Accounting Standards Update, or ASU, 2020-06, which simplifies&lt;/span&gt; the accounting for convertible debt instruments&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. See Note 2, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Polices&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; font-style: italic;"&gt;Convertible Debt, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for details of our adoption of this guidance. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended &lt;/span&gt;December 31, 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.&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 our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;). We formed Akcea in December 2014. &lt;/span&gt;In July 2017, Akcea completed an &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;initial public offering, or IPO, which reduced our ownership of Akcea&#x2019;s common stock below &lt;/span&gt;100 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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;We 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;
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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;We prepared the unaudited interim condensed consolidated financial statements for the &lt;/span&gt;three months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;March 31, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on the same basis as the audited financial statements for the year ended &lt;/span&gt;December 31, 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, with the exception of our retrospective adoption of Accounting Standards Update, or ASU, 2020-06, which simplifies&lt;/span&gt; the accounting for convertible debt instruments&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. See Note 2, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Polices&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; font-style: italic;"&gt;Convertible Debt, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for details of our adoption of this guidance. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended &lt;/span&gt;December 31, 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.&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: 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 condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;). We formed Akcea in December 2014. &lt;/span&gt;In July 2017, Akcea completed an &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;initial public offering, or IPO, which reduced our ownership of Akcea&#x2019;s common stock below &lt;/span&gt;100 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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;We 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;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2.&#160; Significant Accounting Policies&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue Recognition&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="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 condensed 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: TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the United States, or U.S., through the first quarter of 2021, we sold TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that took title to TEGSEDI. The 3PL was our sole customer in the U.S. The 3PL then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In Europe, through 2020, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors. In January 2021, we began commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. In April 2021, we expanded our distribution agreement with Sobi to also include commercializing TEGSEDI in North America. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our collaboration agreement with PTC, PTC is responsible for 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;See &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note 5, &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;, for collaborations with substantive changes that occurred in 2021. Additionally, see &lt;/span&gt;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;, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for a summary of each of our material 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;&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="z8d9a9d8d26f2470084b2214919ea76f3" style="font-family: 'Times New Roman', 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: left;"&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: left; 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="z04a79cf7e5944fadb3a8981b10c12546" style="font-family: 'Times New Roman', 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: left;"&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="z827d7211bc0149798f5246535042da00" style="font-family: 'Times New Roman', 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: left;"&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="z2020479c9eb14102b1b647520bcb9a04" style="font-family: 'Times New Roman', 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="z95ce7f6c09a443e2a4a91ca387fc7742" style="font-family: 'Times New Roman', 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: left;"&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="zc3bceb6a7e27452084778319a0662fd8" style="font-family: 'Times New Roman', 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: left;"&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;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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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="z3c0093ecffd840baac4436225341455a" style="font-family: 'Times New Roman', 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;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 fourth quarter of 2020, we earned a $20 million milestone payment from AstraZeneca when AstraZeneca initiated a Phase 2b study for ION449, our medicine in development targeting PCSK9 to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION449 was contingent on AstraZeneca initiating a Phase 2b 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;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7ccba0de749c470180bbe33a7b5296ca" style="font-family: 'Times New Roman', 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: left;"&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;Next, we allocate the transaction price to each of our performance obligations. When we have to 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. 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;/div&gt;

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

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

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf833054282184f8f94fe2925c718b8f5" style="font-family: 'Times New Roman', 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="za82200695e6f4da091000235978b8218" style="font-family: 'Times New Roman', 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="z58e5ede32c2e40818bde215370ff85ac" style="font-family: 'Times New Roman', 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="zb77919c030b94f00bca1adbf728104d1" style="font-family: 'Times New Roman', 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="zdd01f114f91341cc97b6cb76d7a27934" style="font-family: 'Times New Roman', 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="z909a9745c8e84b03842a54b6db8f2c18" style="font-family: 'Times New Roman', 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="z166b1a85b2984e09868eb3de11ed32b6" style="font-family: 'Times New Roman', 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="zb9d178113c9d49599ac193e5517205cb" style="font-family: 'Times New Roman', 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="z540eca949f34406e894b37392f60b2e2" style="font-family: 'Times New Roman', 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="z0f9a86263d6b461baaa11b805dd6f7db" style="font-family: 'Times New Roman', 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 style="text-align: justify;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z623228cb8c3f4e0d8b2e145cac1e2f5f" style="font-family: 'Times New Roman', 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;We recognize revenue in one of two 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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For R&amp;amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: 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;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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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: TEGSEDI and WAYLIVRA revenue, 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;Prior to our distribution agreement with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our distribution agreement with Sobi we concluded that our performance obligation is to supply finished goods inventory to Sobi. This performance obligation is a series of distinct activities that are substantially the same because we transfer title using the same criteria each time we ship inventory to Sobi. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#x2019;s net sales of TEGSEDI and WAYLIVRA. Additionally, Sobi does not generally have a right of return.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Reserves for TEGSEDI and WAYLIVRA commercial 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;Prior to our distribution agreement with Sobi, w&lt;/span&gt;e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were 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 reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. 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 TEGSEDI and WAYLIVRA revenue in the corresponding period. See our revenue recognition policy 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;, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA 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;Under our distribution agreement with Sobi, Sobi is financially responsible for any applicable reserves.&lt;/div&gt;

&lt;div&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;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 develop IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt; for the treatment of complement-mediated diseases, we received a $75 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 $75 million upfront payment using an input method over the estimated period of time we are providing 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; 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;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the fourth quarter of 2020, we achieved a $7.5 million milestone payment from Biogen when we advanced a target under our 2018 strategic collaboration. 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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy. 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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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;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 fourth quarter of 2020, we earned a $30 million license fee from AstraZeneca when AstraZeneca licensed ION455, an investigational medicine in development to treat nonalcoholic steatohepatitis, or NASH.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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;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;/div&gt;

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

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; 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="z600efe615cfe4baeaf0ee2e16280295d" style="font-family: 'Times New Roman', 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="zce6c576ad62d45c8942d1f34819e712c" style="font-family: 'Times New Roman', 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 sold at a stand-alone selling price.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative 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;For example, 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. As part of the agreement, Bayer paid us a&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; $&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, 2020&#160;&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="zc3bf1afbdaa6479890cee729adac381a" style="font-family: 'Times New Roman', 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="z6491466c797547d99935f9e949447990" style="font-family: 'Times New Roman', 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="zd5744957b61f43afa2185c49ea11782a" style="font-family: 'Times New Roman', 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: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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 one 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;/div&gt;

&lt;div&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: -18pt; 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 &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3"&gt;one quarter&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of March 31, 2021, approximately 46.8 percent of our contracts receivables were from three significant customers. As of December 31, 2020, approximately 99.5 percent of our contracts receivables were from two significant customers.&lt;/div&gt;

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

&lt;div style="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-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 condensed 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: -18pt; 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 condensed consolidated balance sheet.&lt;/span&gt; During the three months ended&#160;March 31, 2021 and 2020, we recognized $26.0 million and $28.0 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="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Sales&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of sales 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 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; 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 condensed 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 March 31, 2021, 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 condensed 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, 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. These observable price changes resulted in us recognizing 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 condensed consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded 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; 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 condensed 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 March 31, 2021, 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&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 insignificant amount of inventory write-offs for the &lt;/span&gt;three months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;March 31, 2021 and 2020&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;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="z3b9bef3aaaa04c50b422ad84f0a316c5" style="font-family: 'Times 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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,695&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;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;/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;18,197&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;2,096&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;/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;1,906&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,005&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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 condensed 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. 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: justify; margin-left: 36pt; 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 condensed consolidated balance sheet and we expense them as the services are provided.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 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. &lt;/span&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&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; 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 we expect to realize.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&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.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&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 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. We based our determination 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 we expect this 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. We also expect 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 continue to maintain a valuation allowance against all our consolidated U.S. federal and state net deferred tax assets.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the &lt;/span&gt;U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.&lt;/div&gt;

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

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Loss Per Share&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the first quarter of 2021, we computed basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the period. For the first quarter of 2021, we did not have to consider Akcea results separately in our calculation because we owned 100 percent of Akcea for the entire period. Our basic net loss per share for the three months ended March 31, 2021 was $0.64.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 first quarter of 2020, prior to the Akcea Acquisition, we calculated our net loss for Ionis on a stand-alone basis plus our share of Akcea&#x2019;s net loss for the period to determine our total net loss attributable to our common stockholders. To calculate the portion of Akcea&#x2019;s net loss attributable to our ownership, we multiplied Akcea&#x2019;s net loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share is different than our net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the three months ended March 31, 2020, 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="z7b5bf2df83804d43854b69383ccbe9b3" style="font-family: 'Times 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 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;Three months ended March 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; 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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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&#x2019;s&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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&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 Per&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Share Calculation&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(as revised*)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; portion of Akcea&#x2019;s net loss&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;&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%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.42&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(32,674&lt;/div&gt;&lt;/td&gt;
    &lt;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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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;&lt;div style="font-family: 'Times New Roman', Times, 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;(32,674&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" 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; 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%; 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;(7,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" 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;" 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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; 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; 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%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; 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; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,706&lt;/div&gt;&lt;/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;" 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;" 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%; 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;139,429&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;Basic net loss per share&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%; 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;(0.28&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;&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" class="DSPFListTable" id="z890ac6907e984110a10e1f06bbbd806e" style="font-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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;*&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, for further information.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Diluted net loss per share&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three months ended&#160;March 31, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock 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="ze05c20ab8a7a49e99cfabe0891503ad7" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z36c843a3550d4b3e93b2ee38a231b0da" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Note hedges related to the 0.125 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6a7fb101db7048108b6a191da4379108" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z153e5c3b8aac48fe89e372bb8d6e7bfe" style="font-family: 'Times New Roman', 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: left;"&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="z57a1ef50f84c4834ae36de72c9d4698e" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested restricted stock units, or RSUs;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze058b3b556b740b1ba0eec702d6ac87b" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested performance restricted stock units, or PRSUs; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z52559752271c453ba9f59a49aed78045" style="font-family: 'Times New Roman', 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: left;"&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;Additionally as of March 31, 2021, we had warrants related to our 0.125 percent convertible senior notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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; font-style: italic;"&gt;Adoption of ASU 2020-06&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 ASU 2020-06, which simplifies&lt;/span&gt; the accounting for convertible debt 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. We adopted ASU 2020-06 on January 1, 2021 under the full retrospective approach, which required us to revise our prior period financial statements. This guidance impacted our accounting for outstanding convertible debt. As of March 31, 2021, we had &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; outstanding convertible notes, our &lt;/span&gt;0.125 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; senior convertible notes, or &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes, which mature in December 2024, and our &lt;/span&gt;1 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; senior convertible notes, or &lt;/span&gt;1%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes, which mature in November 2021.&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 updated guidance eliminates the cash conversion accounting model we previously followed in Accounting Standard Codification, or ASC, 470-20, which required us to separate each of our convertible debt instruments at issuance into two units of accounting, a liability component, based on our nonconvertible debt borrowing rate at issuance, and an equity component. Under ASU 2020-06, we now account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. Since we adopted ASU 2020-06 using the full retrospective approach, we were required to apply the guidance to all convertible debt instruments we had outstanding as of January 1, 2019. We recomputed the basis of each convertible debt instrument as if we accounted for each as a single unit of accounting at issuance. This update included recalculating the amortization of debt issuance costs using an updated effective interest rate. As a result of adopting ASU 2020-06, we recorded a cumulative adjustment to decrease our additional paid in capital and our accumulated deficit at January 1, 2019. We have updated these financial statements to reflect the cumulative adjustment for the periods presented. We have labeled our prior period financial statements &#x201c;as revised&#x201d; to indicate the change required under the new accounting guidance. Below is a summary of the change in our balance sheet at December 31, 2020 and statement of operations from our first quarter 2020 under the ASC 470-20 legacy guidance compared to the new ASU 2020-06 guidance we adopted:&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 adjustments we made to the condensed consolidated balance sheet we originally reported at December 31, 2020 to adopt ASU 2020-06 (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zec17e05117e1400f90bc7141e80f65b8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;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; 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;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293,161&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,648&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;308,809&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent convertible senior notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;455,719&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84,417&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;540,136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additional paid-in-capital&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,113,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(218,127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,895,519&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,249,368&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;118,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,131,306&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;Under ASU 2020-06, our revised ending balances for our 1% Notes and 0.125% Notes as of December 31, 2020 represent the principal balance of each convertible debt instrument less debt issuance costs. Additionally, because we have deferred tax assets related to our convertible debt instruments, we also adjusted these amounts as part of our adoption of ASU 2020-06. However, because we have a full valuation allowance on our deferred tax assets, there was no impact to our condensed consolidated balance sheet related to 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;The following table summarizes the adjustments we made to the condensed consolidated statement of operations we originally reported at March 31, 2020 to adopt ASU 2020-06 (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc88c3f1e063e47dc85bc6ded89479623" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;Three Months Ended March 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; 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;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,990&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,783&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,207&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss before income tax benefit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(61,737&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,783&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(52,954&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income tax benefit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,257&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(185&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,072&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(58,480&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(49,882&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(48,226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,628&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic and diluted net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.35&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.07&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.28&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;/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;Under ASU 2020-06, our revised interest expense is lower as we are no longer recording non-cash interest expense related to a debt discount. This decrease was partially offset by the increase in interest expense related to the amortization of debt issuance costs because we no longer allocate a portion of our debt issuance costs to stockholders&#x2019; equity at issuance. Instead, the entire debt issuance costs were recorded as a contra-liability on our condensed consolidated balance sheet at issuance and we are amortizing them over the contractual term using an updated effective interest rate. Our updated effective interest rates for our 1% Notes and 0.125% Notes were 1.4 percent and 0.5 percent, 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;The following tables summarize the adjustments we made to our condensed consolidated statements of stockholders&#x2019; equity we originally reported at December 31, 2020 and 2019 to adopt ASU 2020-06 (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zbd467850ae924fb5b960ceafc6f21552" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;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; 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;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additional paid-in-capital&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,113,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(218,127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,895,519&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,249,368&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;118,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,131,306&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stockholders' equity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;843,347&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(100,065&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;743,282&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;table cellpadding="0" cellspacing="0" id="z645e923d13f9452783b88b08a82563ef" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additional paid-in-capital&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,203,778&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(218,128&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,985,650&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(707,534&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;111,039&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(596,495&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;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stockholders' equity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,684,547&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(107,089&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,577,458&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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 in December 2019, 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 condensed 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="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Segment Information&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. In October 2020, we acquired the remaining common stock of Akcea that we did not own and fully integrated Akcea&#x2019;s operations into ours as of January 1, 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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 condensed 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. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our 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;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.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions. During the three months ended&#160;March 31, 2021 and 2020, we did not grant any stock options or RSUs to our Board of Directors. For the three months ended&#160;March 31, 2021 and 2020, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" id="zb50774a8db064a76b4654db166588143" style="font-family: 'Times 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;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;March 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;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;1.6&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: 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;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;/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;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;55.1&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;58.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; 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;4.9 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.7 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div 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;ESPP:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z88183c7105e442c8a19d7f09035af980" style="font-family: 'Times 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;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;March 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;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;0.1&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;1.1&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: 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;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;/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;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;39.1&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;47.2&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: left; 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;/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;RSU&#x2019;s:&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. RSUs granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees for the three months ended&#160;March 31, 2021 was $62.02 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;PRSU&#x2019;s:&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning in 2020, we added performance-based restricted stock units, or PRSU, awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Under the terms of the grants, &lt;span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"&gt;&lt;span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"&gt;&lt;span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd"&gt;one third&lt;/span&gt;&lt;/span&gt;&lt;/span&gt; of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero percentto 150 percent of the target number depending on our relative TSR.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined the fair value of Dr. Monia&#x2019;s PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to Dr. Monia for the three months ended March 31, 2021 was $77.17 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;The following table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2021 and 2020 (in thousands).&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;table cellpadding="0" cellspacing="0" id="z568b9f2af42c4a9096bdd2cc2d011e45" style="font-family: 'Times 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;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;March 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; 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;Cost of sales&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;237&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Research, development and patent expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,899&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,556&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,780&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,997&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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: left; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;37,861&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;40,790&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of March 31, 2021, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $101.8 million, $109.6 million and $3.8 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized non-cash stock-based compensation expense for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.4 years, 1.8 years and 1.7 years, 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; 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;As disclosed in the &#x201c;Convertible Debt&#x201d; policy above within this footnote, we adopted the simplified accounting for convertible debt instrument guidance (ASU 2020-06) on January 1, 2021. Refer to the section above for the impact of adoption. We do not expect any other recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:SignificantAccountingPoliciesTextBlock>
    <us-gaap:RevenueFromContractWithCustomerPolicyTextBlock
      contextRef="c20210101to20210331"
      id="Text_23dcd0c53d73416a92d74f38fe21501a">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Revenue Recognition&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="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 condensed 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: TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the United States, or U.S., through the first quarter of 2021, we sold TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that took title to TEGSEDI. The 3PL was our sole customer in the U.S. The 3PL then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In Europe, through 2020, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors. In January 2021, we began commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. In April 2021, we expanded our distribution agreement with Sobi to also include commercializing TEGSEDI in North America. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our collaboration agreement with PTC, PTC is responsible for 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;See &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note 5, &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;, for collaborations with substantive changes that occurred in 2021. Additionally, see &lt;/span&gt;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;, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for a summary of each of our material 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;&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="z8d9a9d8d26f2470084b2214919ea76f3" style="font-family: 'Times New Roman', 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: left;"&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: left; 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="z04a79cf7e5944fadb3a8981b10c12546" style="font-family: 'Times New Roman', 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: left;"&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="z827d7211bc0149798f5246535042da00" style="font-family: 'Times New Roman', 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: left;"&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="z2020479c9eb14102b1b647520bcb9a04" style="font-family: 'Times New Roman', 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="z95ce7f6c09a443e2a4a91ca387fc7742" style="font-family: 'Times New Roman', 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: left;"&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="zc3bceb6a7e27452084778319a0662fd8" style="font-family: 'Times New Roman', 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: left;"&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;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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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="z3c0093ecffd840baac4436225341455a" style="font-family: 'Times New Roman', 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;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 fourth quarter of 2020, we earned a $20 million milestone payment from AstraZeneca when AstraZeneca initiated a Phase 2b study for ION449, our medicine in development targeting PCSK9 to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION449 was contingent on AstraZeneca initiating a Phase 2b 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;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7ccba0de749c470180bbe33a7b5296ca" style="font-family: 'Times New Roman', 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: left;"&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;Next, we allocate the transaction price to each of our performance obligations. When we have to 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. 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;/div&gt;

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

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

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zf833054282184f8f94fe2925c718b8f5" style="font-family: 'Times New Roman', 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="za82200695e6f4da091000235978b8218" style="font-family: 'Times New Roman', 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="z58e5ede32c2e40818bde215370ff85ac" style="font-family: 'Times New Roman', 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="zb77919c030b94f00bca1adbf728104d1" style="font-family: 'Times New Roman', 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="zdd01f114f91341cc97b6cb76d7a27934" style="font-family: 'Times New Roman', 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="z909a9745c8e84b03842a54b6db8f2c18" style="font-family: 'Times New Roman', 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="z166b1a85b2984e09868eb3de11ed32b6" style="font-family: 'Times New Roman', 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="zb9d178113c9d49599ac193e5517205cb" style="font-family: 'Times New Roman', 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="z540eca949f34406e894b37392f60b2e2" style="font-family: 'Times New Roman', 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="z0f9a86263d6b461baaa11b805dd6f7db" style="font-family: 'Times New Roman', 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 style="text-align: justify;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z623228cb8c3f4e0d8b2e145cac1e2f5f" style="font-family: 'Times New Roman', 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;We recognize revenue in one of two 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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For R&amp;amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: 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;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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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: TEGSEDI and WAYLIVRA revenue, 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;Prior to our distribution agreement with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our distribution agreement with Sobi we concluded that our performance obligation is to supply finished goods inventory to Sobi. This performance obligation is a series of distinct activities that are substantially the same because we transfer title using the same criteria each time we ship inventory to Sobi. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#x2019;s net sales of TEGSEDI and WAYLIVRA. Additionally, Sobi does not generally have a right of return.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Reserves for TEGSEDI and WAYLIVRA commercial 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;Prior to our distribution agreement with Sobi, w&lt;/span&gt;e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were 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 reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. 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 TEGSEDI and WAYLIVRA revenue in the corresponding period. See our revenue recognition policy 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;, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA 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;Under our distribution agreement with Sobi, Sobi is financially responsible for any applicable reserves.&lt;/div&gt;

&lt;div&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;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 develop IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt; for the treatment of complement-mediated diseases, we received a $75 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 $75 million upfront payment using an input method over the estimated period of time we are providing 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; 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;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the fourth quarter of 2020, we achieved a $7.5 million milestone payment from Biogen when we advanced a target under our 2018 strategic collaboration. 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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy. 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;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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;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 fourth quarter of 2020, we earned a $30 million license fee from AstraZeneca when AstraZeneca licensed ION455, an investigational medicine in development to treat nonalcoholic steatohepatitis, or NASH.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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;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;/div&gt;

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

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; 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="z600efe615cfe4baeaf0ee2e16280295d" style="font-family: 'Times New Roman', 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="zce6c576ad62d45c8942d1f34819e712c" style="font-family: 'Times New Roman', 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 sold at a stand-alone selling price.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative 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;For example, 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. As part of the agreement, Bayer paid us a&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; $&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, 2020&#160;&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="zc3bf1afbdaa6479890cee729adac381a" style="font-family: 'Times New Roman', 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="z6491466c797547d99935f9e949447990" style="font-family: 'Times New Roman', 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="zd5744957b61f43afa2185c49ea11782a" style="font-family: 'Times New Roman', 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: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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 one 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;/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: -18pt; 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 &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3"&gt;one quarter&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of March 31, 2021, approximately 46.8 percent of our contracts receivables were from three significant customers. As of December 31, 2020, approximately 99.5 percent of our contracts receivables were from two significant customers.&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: -18pt; 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 condensed 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: -18pt; 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 condensed consolidated balance sheet.&lt;/span&gt; During the three months ended&#160;March 31, 2021 and 2020, we recognized $26.0 million and $28.0 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.&lt;/div&gt;
</us-gaap:RevenueRecognitionPolicyTextBlock>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20210101to20210331"
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      unitRef="U002">26000000.0</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20200101to20200331"
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      id="Fact_9b7323eabb394f1aa269712264f74431"
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    <us-gaap:CostOfSalesPolicyTextBlock
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      id="Text_a7157f5414bc403797c3de4182f78f4f">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Sales&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of sales 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 sales. &lt;/div&gt;
</us-gaap:CostOfSalesPolicyTextBlock>
    <us-gaap:InvestmentPolicyTextBlock
      contextRef="c20210101to20210331"
      id="Text_2be3f3248a3e4b9897806424f39c50c5">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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 condensed 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 March 31, 2021, 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 condensed 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, 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. These observable price changes resulted in us recognizing 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 condensed consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.&lt;/div&gt;
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    <ions:NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued
      contextRef="c20200401to20201231"
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      unitRef="U009">3</ions:NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued>
    <us-gaap:GainLossOnInvestments
      contextRef="c20200401to20200630_FinancialInstrumentAxis_DynacureSasMember"
      decimals="-5"
      id="Fact_db63fed8d9ef462ba313eb95dec39cc7"
      unitRef="U002">6300000</us-gaap:GainLossOnInvestments>
    <us-gaap:GainLossOnInvestments
      contextRef="c20200401to20200630_FinancialInstrumentAxis_SuzhouRiboLifeScienceCoLtdMember"
      decimals="-5"
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      unitRef="U002">3000000.0</us-gaap:GainLossOnInvestments>
    <us-gaap:GainLossOnInvestments
      contextRef="c20200401to20200630_FinancialInstrumentAxis_AroBiotherapeuticsMember"
      decimals="-5"
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      unitRef="U002">5500000</us-gaap:GainLossOnInvestments>
    <us-gaap:InventoryPolicyTextBlock
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      id="Text_7383a8eea0944a5fa271be67a4f6a1f6">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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 condensed 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 March 31, 2021, 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&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 insignificant amount of inventory write-offs for the &lt;/span&gt;three months ended&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;March 31, 2021 and 2020&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;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="z3b9bef3aaaa04c50b422ad84f0a316c5" style="font-family: 'Times 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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,695&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;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;/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;18,197&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;2,096&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;/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;1,906&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,005&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;/tr&gt;
&lt;/table&gt;
</us-gaap:InventoryPolicyTextBlock>
    <us-gaap:ScheduleOfInventoryCurrentTableTextBlock
      contextRef="c20210101to20210331"
      id="Text_36cd1b45dfff4b728da90ffcc303bb51">
&lt;div style="display:none;"&gt;&lt;br/&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="z3b9bef3aaaa04c50b422ad84f0a316c5" style="font-family: 'Times 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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,695&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;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;/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;18,197&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;2,096&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;/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;1,906&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,005&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfInventoryCurrentTableTextBlock>
    <us-gaap:InventoryRawMaterials
      contextRef="c20210331_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_3043726b7f0d40479abbe8c68900b93f"
      unitRef="U002">10695000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20201231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_6cec13c5f4334a1ba6216a6bc406747c"
      unitRef="U002">9206000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20210331_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_4a8280762bb1470eace824e402d6b623"
      unitRef="U002">7502000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20201231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_cf1accaf2b004921b424e5cd65e40c1f"
      unitRef="U002">7502000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20210331"
      decimals="-3"
      id="Fact_9975fb0b2fa74f9e8ab81ebad8fb2237"
      unitRef="U002">18197000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20201231"
      decimals="-3"
      id="Fact_e3f1efde1cdb414796dec720e17eac54"
      unitRef="U002">16708000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20210331"
      decimals="-3"
      id="Fact_e7c4b729eb5c4047a12ddaf1f657b647"
      unitRef="U002">2096000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20201231"
      decimals="-3"
      id="Fact_182d548d120f4e1daae74044c3e1bbe5"
      unitRef="U002">2252000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20210331"
      decimals="-3"
      id="Fact_b21c128f10e14f89b4963ecd92676ea1"
      unitRef="U002">1906000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20201231"
      decimals="-3"
      id="Fact_70a3a016ecb849cd9021230823cf224d"
      unitRef="U002">3005000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryNet
      contextRef="c20210331"
      decimals="-3"
      id="Fact_6f6a7ebaae1b4d95ace7fcfcf1fba210"
      unitRef="U002">22199000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20201231"
      decimals="-3"
      id="Fact_3e4c02edf53745679ae7e698216e7837"
      unitRef="U002">21965000</us-gaap:InventoryNet>
    <us-gaap:LesseeLeasesPolicyTextBlock
      contextRef="c20210101to20210331"
      id="Text_0f3cb817b91e46c1811cb95b2cd53633">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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 condensed 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. 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:ResearchAndDevelopmentExpensePolicy
      contextRef="c20210101to20210331"
      id="Text_d2e79a616c5149af971d3c0c1c8a1bfb">
&lt;div style="display:none;"&gt;&lt;br/&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 condensed consolidated balance sheet and we expense them as the services are provided.&lt;/div&gt;
</us-gaap:ResearchAndDevelopmentExpensePolicy>
    <us-gaap:IntangibleAssetsFiniteLivedPolicy
      contextRef="c20210101to20210331"
      id="Text_eae0e633d40249c1b8d1ca3267edd5ca">
&lt;div style="display:none;"&gt;&lt;br/&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 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. &lt;/span&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&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;
</us-gaap:IntangibleAssetsFiniteLivedPolicy>
    <us-gaap:IncomeTaxPolicyTextBlock
      contextRef="c20210101to20210331"
      id="Text_f07117ba6b154c219bc9ea7670cbc326">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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 we expect to realize.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&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.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&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 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. We based our determination 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 we expect this 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. We also expect 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 continue to maintain a valuation allowance against all our consolidated U.S. federal and state net deferred tax assets.&lt;/div&gt;
</us-gaap:IncomeTaxPolicyTextBlock>
    <us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock
      contextRef="c20210101to20210331"
      id="Text_f326f7d8eff14d82bfdd56e71f4064a7">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Long-lived 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;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.&lt;/div&gt;
</us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock>
    <us-gaap:UseOfEstimates
      contextRef="c20210101to20210331"
      id="Text_1b675f2ad8574bcb81c03f729eba4aa0">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the &lt;/span&gt;U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.&lt;/div&gt;
</us-gaap:UseOfEstimates>
    <us-gaap:EarningsPerSharePolicyTextBlock
      contextRef="c20210101to20210331"
      id="Text_d8ae7016e11e44938c278329c28c5334">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Loss Per Share&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the first quarter of 2021, we computed basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the period. For the first quarter of 2021, we did not have to consider Akcea results separately in our calculation because we owned 100 percent of Akcea for the entire period. Our basic net loss per share for the three months ended March 31, 2021 was $0.64.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 first quarter of 2020, prior to the Akcea Acquisition, we calculated our net loss for Ionis on a stand-alone basis plus our share of Akcea&#x2019;s net loss for the period to determine our total net loss attributable to our common stockholders. To calculate the portion of Akcea&#x2019;s net loss attributable to our ownership, we multiplied Akcea&#x2019;s net loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share is different than our net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our basic net loss per share for the three months ended March 31, 2020, 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="z7b5bf2df83804d43854b69383ccbe9b3" style="font-family: 'Times 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 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;Three months ended March 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; 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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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&#x2019;s&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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&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 Per&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Share Calculation&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(as revised*)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; portion of Akcea&#x2019;s net loss&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;&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%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.42&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(32,674&lt;/div&gt;&lt;/td&gt;
    &lt;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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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;&lt;div style="font-family: 'Times New Roman', Times, 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;(32,674&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" 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; 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%; 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;(7,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" 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;" 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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; 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; 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%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; 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; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,706&lt;/div&gt;&lt;/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;" 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;" 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%; 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;139,429&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;Basic net loss per share&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%; 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;(0.28&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;&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" class="DSPFListTable" id="z890ac6907e984110a10e1f06bbbd806e" style="font-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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;*&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, for further information.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Diluted net loss per share&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three months ended&#160;March 31, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock 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="ze05c20ab8a7a49e99cfabe0891503ad7" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z36c843a3550d4b3e93b2ee38a231b0da" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Note hedges related to the 0.125 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6a7fb101db7048108b6a191da4379108" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 percent convertible senior notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z153e5c3b8aac48fe89e372bb8d6e7bfe" style="font-family: 'Times New Roman', 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: left;"&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="z57a1ef50f84c4834ae36de72c9d4698e" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested restricted stock units, or RSUs;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze058b3b556b740b1ba0eec702d6ac87b" style="font-family: 'Times New Roman', 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested performance restricted stock units, or PRSUs; and&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z52559752271c453ba9f59a49aed78045" style="font-family: 'Times New Roman', 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: left;"&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;Additionally as of March 31, 2021, we had warrants related to our 0.125 percent convertible senior notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/div&gt;
</us-gaap:EarningsPerSharePolicyTextBlock>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20210331_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_13943e6576ca415a83b7d65c86a49bff"
      unitRef="U003">1</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20210101to20210331"
      decimals="2"
      id="Fact_aab817918ee7462eafc4e0247e0ea5c8"
      unitRef="U004">-0.64</us-gaap:EarningsPerShareBasic>
    <us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock
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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 basic net loss per share for the three months ended March 31, 2020, 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="z7b5bf2df83804d43854b69383ccbe9b3" style="font-family: 'Times 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 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;Three months ended March 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; 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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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&#x2019;s&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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&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 Per&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Share Calculation&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(as revised*)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; portion of Akcea&#x2019;s net loss&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;&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%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.42&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(32,674&lt;/div&gt;&lt;/td&gt;
    &lt;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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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;&lt;div style="font-family: 'Times New Roman', Times, 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;(32,674&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" 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; 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%; 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;(7,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" 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;" 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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; 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; 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%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; 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; 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 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;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,706&lt;/div&gt;&lt;/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;" 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;" 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%; 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;139,429&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;Basic net loss per share&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%; 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;(0.28&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;&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" class="DSPFListTable" id="z890ac6907e984110a10e1f06bbbd806e" style="font-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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;*&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, for further information.&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; 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; font-style: italic;"&gt;Adoption of ASU 2020-06&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 ASU 2020-06, which simplifies&lt;/span&gt; the accounting for convertible debt 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. We adopted ASU 2020-06 on January 1, 2021 under the full retrospective approach, which required us to revise our prior period financial statements. This guidance impacted our accounting for outstanding convertible debt. As of March 31, 2021, we had &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; outstanding convertible notes, our &lt;/span&gt;0.125 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; senior convertible notes, or &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes, which mature in December 2024, and our &lt;/span&gt;1 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; senior convertible notes, or &lt;/span&gt;1%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes, which mature in November 2021.&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 updated guidance eliminates the cash conversion accounting model we previously followed in Accounting Standard Codification, or ASC, 470-20, which required us to separate each of our convertible debt instruments at issuance into two units of accounting, a liability component, based on our nonconvertible debt borrowing rate at issuance, and an equity component. Under ASU 2020-06, we now account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. Since we adopted ASU 2020-06 using the full retrospective approach, we were required to apply the guidance to all convertible debt instruments we had outstanding as of January 1, 2019. We recomputed the basis of each convertible debt instrument as if we accounted for each as a single unit of accounting at issuance. This update included recalculating the amortization of debt issuance costs using an updated effective interest rate. As a result of adopting ASU 2020-06, we recorded a cumulative adjustment to decrease our additional paid in capital and our accumulated deficit at January 1, 2019. We have updated these financial statements to reflect the cumulative adjustment for the periods presented. We have labeled our prior period financial statements &#x201c;as revised&#x201d; to indicate the change required under the new accounting guidance. Below is a summary of the change in our balance sheet at December 31, 2020 and statement of operations from our first quarter 2020 under the ASC 470-20 legacy guidance compared to the new ASU 2020-06 guidance we adopted:&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 adjustments we made to the condensed consolidated balance sheet we originally reported at December 31, 2020 to adopt ASU 2020-06 (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zec17e05117e1400f90bc7141e80f65b8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;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; 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;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293,161&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,648&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;308,809&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent convertible senior notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;455,719&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84,417&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;540,136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additional paid-in-capital&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,113,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(218,127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,895,519&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,249,368&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;118,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,131,306&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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;Under ASU 2020-06, our revised ending balances for our 1% Notes and 0.125% Notes as of December 31, 2020 represent the principal balance of each convertible debt instrument less debt issuance costs. Additionally, because we have deferred tax assets related to our convertible debt instruments, we also adjusted these amounts as part of our adoption of ASU 2020-06. However, because we have a full valuation allowance on our deferred tax assets, there was no impact to our condensed consolidated balance sheet related to 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;The following table summarizes the adjustments we made to the condensed consolidated statement of operations we originally reported at March 31, 2020 to adopt ASU 2020-06 (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc88c3f1e063e47dc85bc6ded89479623" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;Three Months Ended March 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; 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;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,990&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,783&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,207&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss before income tax benefit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(61,737&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,783&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(52,954&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income tax benefit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,257&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(185&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,072&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(58,480&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(49,882&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(48,226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,628&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic and diluted net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.35&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.07&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.28&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;/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;Under ASU 2020-06, our revised interest expense is lower as we are no longer recording non-cash interest expense related to a debt discount. This decrease was partially offset by the increase in interest expense related to the amortization of debt issuance costs because we no longer allocate a portion of our debt issuance costs to stockholders&#x2019; equity at issuance. Instead, the entire debt issuance costs were recorded as a contra-liability on our condensed consolidated balance sheet at issuance and we are amortizing them over the contractual term using an updated effective interest rate. Our updated effective interest rates for our 1% Notes and 0.125% Notes were 1.4 percent and 0.5 percent, 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;The following tables summarize the adjustments we made to our condensed consolidated statements of stockholders&#x2019; equity we originally reported at December 31, 2020 and 2019 to adopt ASU 2020-06 (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zbd467850ae924fb5b960ceafc6f21552" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;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; 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;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additional paid-in-capital&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,113,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(218,127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,895,519&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,249,368&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;118,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,131,306&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stockholders' equity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;843,347&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(100,065&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;743,282&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;table cellpadding="0" cellspacing="0" id="z645e923d13f9452783b88b08a82563ef" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additional paid-in-capital&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,203,778&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(218,128&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,985,650&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(707,534&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;111,039&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(596,495&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;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stockholders' equity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,684,547&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(107,089&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,577,458&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the adjustments we made to the condensed consolidated balance sheet we originally reported at December 31, 2020 to adopt ASU 2020-06 (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zec17e05117e1400f90bc7141e80f65b8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;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; 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;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293,161&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,648&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;308,809&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent convertible senior notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;455,719&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84,417&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;540,136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additional paid-in-capital&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,113,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(218,127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,895,519&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,249,368&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;118,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,131,306&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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 summarizes the adjustments we made to the condensed consolidated statement of operations we originally reported at March 31, 2020 to adopt ASU 2020-06 (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zc88c3f1e063e47dc85bc6ded89479623" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;Three Months Ended March 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; 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;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,990&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,783&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,207&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss before income tax benefit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(61,737&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,783&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(52,954&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income tax benefit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,257&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(185&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,072&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(58,480&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(49,882&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(48,226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,598&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,628&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic and diluted net loss per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.35&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.07&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.28&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;/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 tables summarize the adjustments we made to our condensed consolidated statements of stockholders&#x2019; equity we originally reported at December 31, 2020 and 2019 to adopt ASU 2020-06 (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zbd467850ae924fb5b960ceafc6f21552" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;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; 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;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additional paid-in-capital&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,113,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(218,127&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,895,519&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,249,368&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;118,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(1,131,306&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stockholders' equity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;843,347&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(100,065&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;743,282&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;table cellpadding="0" cellspacing="0" id="z645e923d13f9452783b88b08a82563ef" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Previously&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Reported&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;ASU 2020-06&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Adjustment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;As Revised&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additional paid-in-capital&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,203,778&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(218,128&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,985,650&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accumulated deficit&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(707,534&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;111,039&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(596,495&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;&lt;div style="font-family: 'Times New 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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total stockholders' equity&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,684,547&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(107,089&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,577,458&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="text-align: justify; text-indent: 36pt; 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;

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&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 in December 2019, 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 condensed 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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&lt;div&gt;&lt;br/&gt;&lt;/div&gt;

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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. In October 2020, we acquired the remaining common stock of Akcea that we did not own and fully integrated Akcea&#x2019;s operations into ours as of January 1, 2021.&lt;/div&gt;
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&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 condensed 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. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP.&lt;/div&gt;

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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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.&lt;/div&gt;

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

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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.&lt;/div&gt;

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

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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions. During the three months ended&#160;March 31, 2021 and 2020, we did not grant any stock options or RSUs to our Board of Directors. For the three months ended&#160;March 31, 2021 and 2020, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

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&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Options:&lt;/div&gt;

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  &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;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;1.6&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: 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;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;/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;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;55.1&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;58.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; 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;4.9 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.7 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div 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;ESPP:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="z88183c7105e442c8a19d7f09035af980" style="font-family: 'Times 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;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;March 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;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;0.1&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;1.1&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: 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;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;/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;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;39.1&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;47.2&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: left; 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;/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;RSU&#x2019;s:&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. RSUs granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees for the three months ended&#160;March 31, 2021 was $62.02 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;PRSU&#x2019;s:&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning in 2020, we added performance-based restricted stock units, or PRSU, awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Under the terms of the grants, &lt;span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"&gt;&lt;span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"&gt;&lt;span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd"&gt;one third&lt;/span&gt;&lt;/span&gt;&lt;/span&gt; of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero percentto 150 percent of the target number depending on our relative TSR.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined the fair value of Dr. Monia&#x2019;s PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to Dr. Monia for the three months ended March 31, 2021 was $77.17 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;The following table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2021 and 2020 (in thousands).&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;table cellpadding="0" cellspacing="0" id="z568b9f2af42c4a9096bdd2cc2d011e45" style="font-family: 'Times 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;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;March 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; 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;Cost of sales&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;237&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Research, development and patent expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,899&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,556&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,780&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,997&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="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;
    &lt;td style="vertical-align: bottom; width: 76%; 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&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;37,861&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;40,790&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of March 31, 2021, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $101.8 million, $109.6 million and $3.8 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized non-cash stock-based compensation expense for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.4 years, 1.8 years and 1.7 years, respectively.&lt;/div&gt;
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&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Options:&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" id="zb50774a8db064a76b4654db166588143" style="font-family: 'Times 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;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;March 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;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;1.6&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;
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    &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;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;
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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;
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  &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;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;55.1&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;58.9&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;
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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;4.9 years&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;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="display:none;"&gt;&lt;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;ESPP:&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="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;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;March 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;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;0.1&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;1.1&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: 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;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;/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;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;39.1&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;47.2&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: left; 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;/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 three months ended&#160;March 31, 2021 and 2020 (in thousands).&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;

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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="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;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;March 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; 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;Cost of sales&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;237&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Research, development and patent expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,899&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,556&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative expense&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,780&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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,997&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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: left; 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;37,861&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;40,790&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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; 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;As disclosed in the &#x201c;Convertible Debt&#x201d; policy above within this footnote, we adopted the simplified accounting for convertible debt instrument guidance (ASU 2020-06) on January 1, 2021. Refer to the section above for the impact of adoption. We do not expect any other recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
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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.&#160; 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 March 31, 2021:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z7c460e53f6064325b6b396c3042dae44" style="font-family: 'Times 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: left; text-indent: -9pt; margin-left: 46.8pt; 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;67&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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: left; text-indent: -9pt; margin-left: 46.8pt; 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After two years but within &lt;span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797"&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;13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; 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;&#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;100&lt;/div&gt;&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;/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 March 31, 2021, 87 percent of our available-for-sale securities had a maturity of less than two years.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We invest in available-for-sale securities&lt;/span&gt; with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp;amp; Poor&#x2019;s, or S&amp;amp;P, Moody&#x2019;s or Fitch, respectively.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At March 31, 2021, we had an ownership interest of less than 20 percent in seven private companies and two public companies with which we conduct business. The privately held companies are 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 Antisense Therapeutics Ltd. and ProQR Therapeutics N.V.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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 style="text-align: left;"&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="z6693b4efc48c4fdaaacf5939c037f0c0" style="font-family: 'Times 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; text-indent: -9pt; margin-left: 9pt; 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;&#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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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;&lt;span style="text-decoration: underline;"&gt;Available-for-sale securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;446,816&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,838&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(76&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;448,578&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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: 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;80,703&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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;292&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;80,993&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#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;234,164&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;126&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;234,290&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;&#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: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;121,776&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;220&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;121,974&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div 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;5,137&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;&#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;5,130&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; 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;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;" valign="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;888,596&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;2,476&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;(107&lt;/div&gt;&lt;/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;890,965&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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%; 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;325,335&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,108&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(245&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;328,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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: 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;96,698&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;36&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(164&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;96,570&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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 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;59,030&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;326&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,515&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,571&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,233&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;(20&lt;/div&gt;&lt;/td&gt;
    &lt;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;6,213&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;" valign="bottom"&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;" valign="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;521,811&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;3,551&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;(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;&lt;div style="font-family: 'Times 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;524,873&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,410,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,027&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(596&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,415,838&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Equity securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,514&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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 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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;31,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,514&lt;/div&gt;&lt;/td&gt;
    &lt;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;34,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; 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;" valign="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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,430,181&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,110&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,450,036&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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="zff8613ae861b4a6ba5595d275d904f87" style="font-family: 'Times 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; text-indent: -9pt; margin-left: 9pt; 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;&#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; text-indent: -9pt; margin-left: 9pt; 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;&lt;span style="text-decoration: underline;"&gt;Available-for-sale securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" 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%;" valign="bottom"&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;94,234&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;94,586&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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 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%;" valign="bottom"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,271&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;104,455&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: 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;" valign="bottom"&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;" valign="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;1,025,454&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;2,977&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;(71&lt;/div&gt;&lt;/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;1,028,360&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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%; 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%;" valign="bottom"&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;80,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;185&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;80,275&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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 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%;" valign="bottom"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,779&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(16&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,854&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div 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;" valign="bottom"&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;" valign="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;488,316&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;5,600&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;(69&lt;/div&gt;&lt;/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;493,847&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,513,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Equity securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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: 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;" valign="bottom"&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;31,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,533,544&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,515&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,821&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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; 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="z50ea1d1bc6054ac6969b1083cf8ef6fd" style="font-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; 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;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="z8f50e28fedfe4eef9cf6ee5a1a7c0ccd" style="font-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; 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash equivalents on our condensed 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="z860f6d5bdfcf49cf808f1c8cbb8e1031" style="font-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; 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="z7074f09c0aa945fc813760e477ae0131" style="font-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; 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;.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following is a summary of our investments we consider to be temporarily impaired at &lt;/span&gt;March 31, 2021&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. 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="z8e6e3cb9e4a844ac94194614765f5afe" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;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;Number of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;101&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;233,665&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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%; 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;60,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;(166&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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; 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;52,838&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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;(35&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;297&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-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;76,712&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-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;(47&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;11,343&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;(27&lt;/div&gt;&lt;/td&gt;
    &lt;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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;414&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;435,239&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(596&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:InvestmentTextBlock>
    <us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock
      contextRef="c20210101to20210331"
      id="Text_88180c6e643a4b7eb3d2e8e8e7abb05a">
&lt;div style="display:none;"&gt;&lt;br/&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 March 31, 2021:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z7c460e53f6064325b6b396c3042dae44" style="font-family: 'Times 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: left; text-indent: -9pt; margin-left: 46.8pt; 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;67&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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: left; text-indent: -9pt; margin-left: 46.8pt; 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After two years but within &lt;span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797"&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;13&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; 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;&#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;100&lt;/div&gt;&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;/tr&gt;
&lt;/table&gt;
</us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock>
    <ions:MaximumContractMaturityPeriodRange1
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    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage
      contextRef="c20210331"
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      id="Fact_26a36804df4340729bec0b2f463acda4"
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    <ions:MaximumContractMaturityPeriodRange1
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      id="Fact_3bd993e525784a5398b297b7856fe228">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:MaximumContractMaturityPeriodRange2
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      id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage
      contextRef="c20210331"
      decimals="2"
      id="Fact_b3c2ee50dd694d208197df43360458a9"
      unitRef="U003">0.20</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
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      id="Fact_812c571149d64b329fe4410606d76c7a">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage
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      decimals="2"
      id="Fact_8cd01e7f5688446294ec6f1b2d7e38df"
      unitRef="U003">0.13</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage
      contextRef="c20210331"
      decimals="2"
      id="Fact_6217a171f5784696968b178278e97ffa"
      unitRef="U003">1</ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage
      contextRef="c20210331"
      decimals="2"
      id="Fact_7de0397396204971870c9dfa3dc16f94"
      unitRef="U003">0.87</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20210101to20210331"
      id="Fact_34c87d75876e42c988ffebc06f56b6a3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20210331"
      decimals="INF"
      id="Fact_b7edbc55e46842cb916a4ced56279788"
      unitRef="U008">7</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20210331"
      decimals="INF"
      id="Fact_8144a98eb4174391a5f3065f3f804da4"
      unitRef="U008">2</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock
      contextRef="c20210101to20210331"
      id="Text_b7c74c13c32e406597a8b0ef49047c5a">
&lt;div style="display:none;"&gt;&lt;br/&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 style="text-align: left;"&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="z6693b4efc48c4fdaaacf5939c037f0c0" style="font-family: 'Times 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; text-indent: -9pt; margin-left: 9pt; 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;&#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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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;&lt;span style="text-decoration: underline;"&gt;Available-for-sale securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;446,816&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,838&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(76&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;448,578&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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: 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;80,703&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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;292&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;80,993&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#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;234,164&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;126&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;234,290&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;&#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: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;121,776&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;220&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;121,974&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div 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;5,137&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;&#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;5,130&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; 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;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;" valign="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;888,596&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;2,476&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;(107&lt;/div&gt;&lt;/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;890,965&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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%; 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;325,335&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,108&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(245&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;328,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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: 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;96,698&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;36&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(164&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;96,570&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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 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;59,030&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;326&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59,321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,515&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,571&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,233&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;(20&lt;/div&gt;&lt;/td&gt;
    &lt;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;6,213&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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;" valign="bottom"&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;" valign="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;521,811&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;3,551&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;(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;&lt;div style="font-family: 'Times 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;524,873&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,410,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,027&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(596&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,415,838&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Equity securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,514&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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 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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;31,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,514&lt;/div&gt;&lt;/td&gt;
    &lt;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;34,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; 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;" valign="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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,430,181&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,110&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,450,036&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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="zff8613ae861b4a6ba5595d275d904f87" style="font-family: 'Times 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; text-indent: -9pt; margin-left: 9pt; 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;&#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; text-indent: -9pt; margin-left: 9pt; 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;&lt;span style="text-decoration: underline;"&gt;Available-for-sale securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" 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%;" valign="bottom"&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;94,234&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;94,586&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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 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%;" valign="bottom"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,271&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;104,455&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: 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;" valign="bottom"&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;" valign="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;1,025,454&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;2,977&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;(71&lt;/div&gt;&lt;/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;1,028,360&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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%; 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%;" valign="bottom"&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;80,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;185&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;80,275&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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 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%;" valign="bottom"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,779&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(16&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,854&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div 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;" valign="bottom"&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;" valign="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;488,316&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;5,600&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;(69&lt;/div&gt;&lt;/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;493,847&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,513,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-decoration: underline;"&gt;Equity securities:&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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: 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;" valign="bottom"&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,062&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,938&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;31,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity 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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,533,544&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,515&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,821&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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; 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="z50ea1d1bc6054ac6969b1083cf8ef6fd" style="font-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; 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;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="z8f50e28fedfe4eef9cf6ee5a1a7c0ccd" style="font-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; 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: left;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash equivalents on our condensed 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="z860f6d5bdfcf49cf808f1c8cbb8e1031" style="font-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; 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="z7074f09c0aa945fc813760e477ae0131" style="font-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; 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;.&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following is a summary of our investments we consider to be temporarily impaired at &lt;/span&gt;March 31, 2021&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. 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="z8e6e3cb9e4a844ac94194614765f5afe" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;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;Number of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;101&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;233,665&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(321&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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%; 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;60,681&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;(166&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; 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;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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; 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;52,838&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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;(35&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;297&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-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;76,712&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-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;(47&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;11,343&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;(27&lt;/div&gt;&lt;/td&gt;
    &lt;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; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;414&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;435,239&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(596&lt;/div&gt;&lt;/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;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;4.&#160; 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following tables present the major security types we held at &lt;/span&gt;March 31, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;December 31, 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; that we regularly measure and carry at fair value. As of &lt;/span&gt;March 31, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;December 31, 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;we did not have any investments that we valued using Level 3 inputs&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="za1eadbc76bb84a258f94379bc57e4ff9" style="font-family: 'Times 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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;372,050&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;372,050&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;776,776&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;776,776&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;177,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;177,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;293,611&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293,611&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;156,545&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;156,545&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (3)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,343&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;11,343&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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. (4)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;1,791,086&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;668,859&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,122,227&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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="z8fa75e640870498fb69868b78d69ca2a" style="font-family: 'Times 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 (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 (5)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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 (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 (3)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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. (4)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following footnotes reference lines on our condensed consolidated balance sheet:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za9f1e79f3970431d9fdf89fa7695a2cd" style="font-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; 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 condensed 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="zabaf85a12041423a8a0f27cb847986b1" style="font-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; 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 was included in cash and cash equivalents, with the difference 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="z6f9607f6620b4bbd9672800078d88f17" style="font-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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments.&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="z77f49d1f8884459da3bd041fd3da0886" style="font-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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in other current assets on our condensed 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="z577adaddd59340a88de9768ca9301d05" style="font-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; 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;$17.5 million included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed 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;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Convertible Notes&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our 1% Notes and 0.125% Notes had a fair value of $314.6 million and $527.3 million at March 31, 2021, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.&lt;/div&gt;
</us-gaap:FairValueDisclosuresTextBlock>
    <us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock
      contextRef="c20210101to20210331"
      id="Text_4fcb23a6feef4ee98e2536dc2be3fd44">
&lt;div style="display:none;"&gt;&lt;br/&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 present the major security types we held at &lt;/span&gt;March 31, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;December 31, 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; that we regularly measure and carry at fair value. As of &lt;/span&gt;March 31, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;December 31, 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;we did not have any investments that we valued using Level 3 inputs&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="za1eadbc76bb84a258f94379bc57e4ff9" style="font-family: 'Times 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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;372,050&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;372,050&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;776,776&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;776,776&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;177,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;177,563&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;293,611&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;293,611&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;156,545&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;156,545&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (3)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,343&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;11,343&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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. (4)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,198&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;1,791,086&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;668,859&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,122,227&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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="z8fa75e640870498fb69868b78d69ca2a" style="font-family: 'Times 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 (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 (5)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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 (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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 (3)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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. (4)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following footnotes reference lines on our condensed consolidated balance sheet:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" id="za9f1e79f3970431d9fdf89fa7695a2cd" style="font-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; 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 condensed 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="zabaf85a12041423a8a0f27cb847986b1" style="font-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; 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 was included in cash and cash equivalents, with the difference 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="z6f9607f6620b4bbd9672800078d88f17" style="font-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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments.&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="z77f49d1f8884459da3bd041fd3da0886" style="font-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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in other current assets on our condensed 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="z577adaddd59340a88de9768ca9301d05" style="font-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; 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;$17.5 million included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;5.&#160; Collaborative Arrangements and Licensing 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Below, we have included our Biogen collaboration, which is our only collaboration with substantive changes during &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2021&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;December 31, 2020&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="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; font-weight: bold;"&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 March 31, 2021, we have received $2.9 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three months ended March 31, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

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

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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
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    &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;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;66.0&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: 76%; 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;18.1&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;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;21.4&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;
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    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue from our relationship with Biogen&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;78.1&lt;/div&gt;&lt;/td&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;87.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;70&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&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 condensed consolidated balance sheet at March 31, 2021 and December 31, 2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;included deferred revenue of $447.7 million and $465.8 million, respectively, related to our relationship with 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;During the first three months of 2021, we did not have any changes to our performance obligations, transaction price or the timing in which we expect to recognize revenue under 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In April 2021, we achieved a $10 million milestone payment from Biogen when Biogen advanced ION541, an investigational medicine targeting ataxin 2 to treat patients with ALS. We will achieve the next payment of $8 million if Biogen advances one of the medicines under our 2013 strategic neurology collaboration.&lt;/div&gt;
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&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the three months ended March 31, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

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

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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="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;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;March 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;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;66.0&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: 76%; 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;18.1&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;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;21.4&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;
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    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue from our relationship with Biogen&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;78.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;87.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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: 27pt; 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;70&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;66&lt;/div&gt;&lt;/td&gt;
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  &lt;/tr&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;6. 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; font-style: italic;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0 Percent&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Convertible Senior Notes and Call Spread&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 April 2021, we completed a $632.5 million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the 0 percent convertible senior notes, or 0% Notes, to repurchase $247.9 million in principal of our 1% Notes for $257.0 million.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Following the closing of the debt transaction in April 2021, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes outstanding (amounts in millions except interest rate and price per share data):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z88e151c0fc7e49d29682b6fa6b7ce8ae" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" 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;" 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;&lt;span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde"&gt;April 2026&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The call spread cost us $46.9 million, of which $136.7 million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0% Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not have any rights with respect to the note hedges and warrants.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;0.125 Percent Convertible Senior Notes and Call Spread&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At March 31, 2021, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zdec28b8ce2fa4927b412e34f0d8bfaa8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0.125% Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;548.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" 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;" 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;&lt;span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec"&gt;December 2024&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83.28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;123.38&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8.1&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;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In conjunction with the issuance of our &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes in December 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our &lt;/span&gt;0.125% Notes by increasing the effective conversion price on our 0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We increased our effective conversion price to $&lt;/span&gt;123.38&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; with the same number of underlying shares as our &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes. The call spread cost us $&lt;/span&gt;52.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, of which $&lt;/span&gt;108.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million was for the note hedge purchase, offset by $&lt;/span&gt;56.1&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million we received for selling the warrants. Similar to our &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The note hedges will expire upon maturity of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The holders of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; do not have any rights with respect to the note hedges and warrants.&lt;/span&gt;&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the amount paid for the note hedges and the amount received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1 Percent Convertible Senior Notes&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At March 31, 2021, we had the following 1% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z18f2e28c3bf848fab4205a897b0abb11" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;" 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;" 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;&lt;span style="-sec-ix-hidden:Fact_cca8f6878ebf4cc88a7c1b64303ba443"&gt;November 2021&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.8&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;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In April 2021, we repurchased $247.9 million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result, in April 2021, the remaining principal outstanding for our 1% Notes was $62.0 million, resulting in 0.9 million shares of common stock subject to conversion. As a result of the repurchase, we reclassified the repurchased portion of our 1% Notes from current to non-current liabilities on our condensed consolidated balance sheet as of March 31, 2021 because we replaced this portion of our outstanding debt with long-term 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Other Terms of Convertible Senior Notes&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The 0%, 0.125% and 1% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.&lt;/div&gt;
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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;Following the closing of the debt transaction in April 2021, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes outstanding (amounts in millions except interest rate and price per share data):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z88e151c0fc7e49d29682b6fa6b7ce8ae" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" 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;" 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;&lt;span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde"&gt;April 2026&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At March 31, 2021, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="zdec28b8ce2fa4927b412e34f0d8bfaa8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0.125% Notes&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
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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;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;" 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;" 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;&lt;span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec"&gt;December 2024&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83.28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;123.38&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8.1&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;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At March 31, 2021, we had the following 1% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z18f2e28c3bf848fab4205a897b0abb11" 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="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1% 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;
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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;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;" 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;" 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;&lt;span style="-sec-ix-hidden:Fact_cca8f6878ebf4cc88a7c1b64303ba443"&gt;November 2021&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;
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    &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;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;
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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;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;
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    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.8&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;
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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. Severance and Retention Costs&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;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;As a result of the Akcea Acquisition in October 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total estimated severance and retention expenses related to the Akcea Acquisition (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z2c6fe3da616b4ce5a57305457936e51c" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Severance and Retention Expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total estimated 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;28.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expenses incurred in the three months ended December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15.3&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;Expenses incurred in the three months ended March 31, 2021&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;5.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Remaining estimated expenses to be recognized through October 2021&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;7.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;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 table summarizes our severance and retention expenses related to the Akcea Acquisition that we recognized during the three months ended&#160;March 31, 2021 (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z66701bad96c440b099dd3e06c59b7285" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Research, development and patent 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;2.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative 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;2.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; 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;5.4&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;&#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 amounts related to the Akcea Acquisition that we included in accrued compensation for the period indicated (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z5b489fcb281c4c45bd3bb47f2580dae7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Beginning balance&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;14.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 16.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts expensed during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.1&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;&#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; text-indent: 16.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Reserve adjustments 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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.7&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: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net amount expensed during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9.0&lt;/div&gt;&lt;/td&gt;
    &lt;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;Ending balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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 reserve adjustments during the period primarily related to forfeitures of severance and retention payments as a result of employee terminations before they earned the 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; font-style: italic;"&gt;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;As a result of restructuring our European operations, or Restructured European Operations, in December 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total severance and retention expenses related to our Restructured European Operations (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z4017ce63a44d40988c5306fc8d86c8e2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Severance and Retention Expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total estimated 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;13.6&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: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expenses incurred in the three months ended December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.5&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;Expenses incurred in the three months ended March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Remaining estimated expenses through October 2021&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;0.4&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;

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

&lt;div style="display:none;"&gt;&lt;br/&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 expenses related to our Restructured European Operations that we recognized during the three months ended&#160;March 31, 2021 (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z88d9ea5d72574713a598d1c5c92f65ca" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Research, development and patent 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;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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative 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;0.6&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; 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;0.7&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 amounts related to our Restructured European operations that we included in accrued compensation for the periods indicated (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z29b1189fd5b24a6ca7fd9d3c5320b342" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Beginning balance&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;12.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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; text-indent: 18.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts expensed during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 18.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Reserve adjustments 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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net amount expensed during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;&#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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11.9&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: 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;Ending balance&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;1.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The reserve adjustments during the period primarily related to tax expense adjustments.&lt;/div&gt;

&lt;div&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;Restructured North American TEGSEDI 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;In April 2021, we entered into a distribution agreement with Sobi for TEGSEDI in North America. Under the terms of the distribution agreement, we will retain the marketing authorizations for TEGSEDI in the U.S. and Canada. We will continue to supply commercial product to Sobi and manage regulatory and manufacturing processes, as well as relationships with key opinion leaders. We will also continue to lead the TEGSEDI global commercial strategy. Sobi will otherwise have responsibility for commercializing TEGSEDI in the U.S. and Canada and will assume these activities by August 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In connection with restructuring our North American TEGSEDI operations, or Restructured North American TEGSEDI Operations, we enacted a plan to reorganize our Akcea workforce in North America to better align with the needs of our business, or the Reorganization Plan, and to focus on our wholly owned pipeline. Under the Reorganization Plan, we expect to incur restructuring charges in the range of $11 million to $14 million principally in the second quarter of 2021.&lt;/div&gt;
</us-gaap:RestructuringAndRelatedActivitiesDisclosureTextBlock>
    <us-gaap:ScheduleOfRestructuringAndRelatedCostsTextBlock
      contextRef="c20210101to20210331_RestructuringCostAndReserveAxis_AkceaAcquisitionMember"
      id="Text_ba4d802303864f588dbee77c690cafb8">
&lt;div style="display:none;"&gt;&lt;br/&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 the Akcea Acquisition in October 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total estimated severance and retention expenses related to the Akcea Acquisition (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z2c6fe3da616b4ce5a57305457936e51c" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Severance and Retention Expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total estimated 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;28.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expenses incurred in the three months ended December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15.3&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;Expenses incurred in the three months ended March 31, 2021&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;5.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&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;Remaining estimated expenses to be recognized through October 2021&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;7.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;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 table summarizes our severance and retention expenses related to the Akcea Acquisition that we recognized during the three months ended&#160;March 31, 2021 (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z66701bad96c440b099dd3e06c59b7285" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Research, development and patent 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;2.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative 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;2.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; 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;5.4&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;&#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 amounts related to the Akcea Acquisition that we included in accrued compensation for the period indicated (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z5b489fcb281c4c45bd3bb47f2580dae7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Beginning balance&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;14.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 16.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts expensed during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.1&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;&#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; text-indent: 16.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Reserve adjustments 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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.7&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;5.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&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; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9.0&lt;/div&gt;&lt;/td&gt;
    &lt;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;
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    &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;Ending balance&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11.1&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;As a result of restructuring our European operations, or Restructured European Operations, in December 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total severance and retention expenses related to our Restructured European Operations (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z4017ce63a44d40988c5306fc8d86c8e2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
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    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Severance and Retention Expenses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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;Total estimated 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;13.6&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;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;Expenses incurred in the three months ended December 31, 2020&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.5&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;
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  &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;Expenses incurred in the three months ended March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
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  &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;Remaining estimated expenses through October 2021&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;0.4&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;

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

&lt;div style="display:none;"&gt;&lt;br/&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 expenses related to our Restructured European Operations that we recognized during the three months ended&#160;March 31, 2021 (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z88d9ea5d72574713a598d1c5c92f65ca" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Research, development and patent 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;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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative 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;0.6&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;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; 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;0.7&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 amounts related to our Restructured European operations that we included in accrued compensation for the periods indicated (in millions):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" id="z29b1189fd5b24a6ca7fd9d3c5320b342" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;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;March 31, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/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;Beginning balance&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;12.4&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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; text-indent: 18.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts expensed during the period&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Document and Entity Information - shares<br></strong></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_dei_SecurityExchangeName', window );">Security Exchange Name</a></td>
<td class="text">NASDAQ<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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>
</tr>
<tr 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_EntityInteractiveDataCurrent', window );">Entity Interactive Data Current</a></td>
<td class="text">Yes<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_EntityFilerCategory', window );">Entity Filer Category</a></td>
<td class="text">Large Accelerated Filer<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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>
</tr>
<tr 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>
</tr>
<tr 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>
</tr>
<tr 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_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">140,963,028<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AmendmentFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</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_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CoverAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CurrentFiscalYearEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:gMonthDayItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_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_DocumentQuarterlyReport">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 quarterly 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 Form 10-Q<br> -Number 240<br> -Section 13<br> -Subsection a-13<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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_DocumentQuarterlyReport</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_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_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_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>14
<FILENAME>R2.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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<body>
<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191058084888">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">$ 414,155<span></span>
</td>
<td class="nump">$ 397,664<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Short-term investments</a></td>
<td class="nump">1,405,840<span></span>
</td>
<td class="nump">1,494,711<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_ContractWithCustomerAssetNetCurrent', window );">Contracts receivable</a></td>
<td class="nump">23,397<span></span>
</td>
<td class="nump">76,204<span></span>
</td>
</tr>
<tr class="re">
<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">22,199<span></span>
</td>
<td class="nump">21,965<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_OtherAssetsCurrent', window );">Other current assets</a></td>
<td class="nump">123,827<span></span>
</td>
<td class="nump">140,163<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">1,989,418<span></span>
</td>
<td class="nump">2,130,707<span></span>
</td>
</tr>
<tr class="ro">
<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">180,413<span></span>
</td>
<td class="nump">181,077<span></span>
</td>
</tr>
<tr class="re">
<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">28,795<span></span>
</td>
<td class="nump">27,937<span></span>
</td>
</tr>
<tr class="ro">
<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">49,925<span></span>
</td>
<td class="nump">50,034<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_Assets', window );">Total assets</a></td>
<td class="nump">2,248,551<span></span>
</td>
<td class="nump">2,389,755<span></span>
</td>
</tr>
<tr class="ro">
<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_AccountsPayableCurrent', window );">Accounts payable</a></td>
<td class="nump">9,506<span></span>
</td>
<td class="nump">17,199<span></span>
</td>
</tr>
<tr class="ro">
<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">29,263<span></span>
</td>
<td class="nump">65,728<span></span>
</td>
</tr>
<tr class="re">
<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">78,766<span></span>
</td>
<td class="nump">90,161<span></span>
</td>
</tr>
<tr class="ro">
<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">1,326<span></span>
</td>
<td class="nump">1,324<span></span>
</td>
</tr>
<tr class="re">
<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 portion of 1 percent convertible senior notes, net</a></td>
<td class="nump">61,816<span></span>
</td>
<td class="nump">308,809<span></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_LongTermObligationsCurrent', window );">Current portion of long-term obligations</a></td>
<td class="nump">7,688<span></span>
</td>
<td class="nump">7,301<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_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred contract revenue</a></td>
<td class="nump">106,740<span></span>
</td>
<td class="nump">108,376<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_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">295,105<span></span>
</td>
<td class="nump">598,898<span></span>
</td>
</tr>
<tr class="re">
<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">401,966<span></span>
</td>
<td class="nump">424,046<span></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_LongTermObligationsNoncurrent', window );">Long-term obligations, less current portion</a></td>
<td class="nump">22,943<span></span>
</td>
<td class="nump">23,409<span></span>
</td>
</tr>
<tr class="re">
<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">60,002<span></span>
</td>
<td class="nump">59,984<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_Liabilities', window );">Total liabilities</a></td>
<td class="nump">1,567,987<span></span>
</td>
<td class="nump">1,646,473<span></span>
</td>
</tr>
<tr class="re">
<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="ro">
<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, 140,924,356 and 140,365,594 shares issued and outstanding at March 31, 2021 (unaudited) and December 31, 2020, respectively</a></td>
<td class="nump">141<span></span>
</td>
<td class="nump">140<span></span>
</td>
</tr>
<tr class="re">
<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">1,925,801<span></span>
</td>
<td class="nump">1,895,519<span></span>
</td>
</tr>
<tr class="ro">
<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">(24,203)<span></span>
</td>
<td class="num">(21,071)<span></span>
</td>
</tr>
<tr class="re">
<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">(1,221,175)<span></span>
</td>
<td class="num">(1,131,306)<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_StockholdersEquity', window );">Total stockholders' equity</a></td>
<td class="nump">680,564<span></span>
</td>
<td class="nump">743,282<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_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">2,248,551<span></span>
</td>
<td class="nump">2,389,755<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_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_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_ConvertibleDebtNoncurrent', window );">Convertible senior notes, net</a></td>
<td class="nump">540,679<span></span>
</td>
<td class="nump">540,136<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_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, net</a></td>
<td class="nump">$ 247,292<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_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>
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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>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>
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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>
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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_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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<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>
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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>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>
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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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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_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_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>
<td style="white-space:nowrap;">us-gaap_RetainedEarningsAccumulatedDeficit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
<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 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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -URI http://asc.fasb.org/extlink&amp;oid=27010918&amp;loc=d3e74512-122707<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://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 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30))<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><br>Reference 7: 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></p></div>
<a href="javascript:void(0);" 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>
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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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<td><strong> Name:</strong></td>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191062319656">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares<br></strong></div></th>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockParOrStatedValuePerShare', window );">Common stock, par value (in dollars per share)</a></td>
<td class="nump">$ 0.001<span></span>
</td>
<td class="nump">$ 0.001<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesAuthorized', window );">Common stock, shares authorized (in shares)</a></td>
<td class="nump">300,000,000<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">140,924,356<span></span>
</td>
<td class="nump">140,365,594<span></span>
</td>
</tr>
<tr class="re">
<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">140,924,356<span></span>
</td>
<td class="nump">140,365,594<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_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>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockParOrStatedValuePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>num:perShareItemType</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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<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
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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> Balance Type:</strong></td>
<td>na</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 );">- 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>
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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>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
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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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<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 );">- 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><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 );">- 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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<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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191062048136">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Mar. 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_RevenuesAbstract', window );"><strong>Revenue:</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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 111,607<span></span>
</td>
<td class="nump">$ 133,367<span></span>
</td>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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 sales</a></td>
<td class="nump">2,578<span></span>
</td>
<td class="nump">2,548<span></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">139,801<span></span>
</td>
<td class="nump">116,952<span></span>
</td>
</tr>
<tr class="ro">
<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">61,199<span></span>
</td>
<td class="nump">74,994<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">203,578<span></span>
</td>
<td class="nump">194,494<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 );">Loss from operations</a></td>
<td class="num">(91,971)<span></span>
</td>
<td class="num">(61,127)<span></span>
</td>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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">4,643<span></span>
</td>
<td class="nump">10,479<span></span>
</td>
</tr>
<tr class="re">
<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">(2,414)<span></span>
</td>
<td class="num">(2,207)<span></span>
</td>
</tr>
<tr class="ro">
<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 income (expenses)</a></td>
<td class="nump">3<span></span>
</td>
<td class="num">(99)<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 );">Loss before income tax (expense) benefit</a></td>
<td class="num">(89,739)<span></span>
</td>
<td class="num">(52,954)<span></span>
</td>
</tr>
<tr class="ro">
<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 (expense) benefit</a></td>
<td class="num">(130)<span></span>
</td>
<td class="nump">3,072<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 loss</a></td>
<td class="num">(89,869)<span></span>
</td>
<td class="num">(49,882)<span></span>
</td>
</tr>
<tr class="ro">
<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 loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">10,254<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_NetIncomeLoss', window );">Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">$ (89,869)<span></span>
</td>
<td class="num">$ (39,628)<span></span>
</td>
</tr>
<tr class="ro">
<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 loss per share (in dollars per share)</a></td>
<td class="num">$ (0.64)<span></span>
</td>
<td class="num">$ (0.28)<span></span>
</td>
</tr>
<tr class="re">
<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 loss per share (in dollars per share)</a></td>
<td class="num">$ (0.64)<span></span>
</td>
<td class="num">$ (0.28)<span></span>
</td>
</tr>
<tr class="ro">
<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 loss per share (in shares)</a></td>
<td class="nump">140,770<span></span>
</td>
<td class="nump">139,429<span></span>
</td>
</tr>
<tr class="re">
<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 loss per share (in shares)</a></td>
<td class="nump">140,770<span></span>
</td>
<td class="nump">139,429<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>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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">$ 84,448<span></span>
</td>
<td class="nump">$ 83,961<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>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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">59,986<span></span>
</td>
<td class="nump">66,008<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 );">TEGSEDI and WAYLIVRA Revenue, Net [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_RevenuesAbstract', window );"><strong>Revenue:</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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">19,838<span></span>
</td>
<td class="nump">15,159<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>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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">4,624<span></span>
</td>
<td class="nump">2,794<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>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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">$ 27,159<span></span>
</td>
<td class="nump">$ 49,406<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>
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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>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
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<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>
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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_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_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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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>
<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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-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>
<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_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>
</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_srt_ProductOrServiceAxis=ions_CommercialMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</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>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191065003752">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Mar. 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_StatementOfIncomeAndComprehensiveIncomeAbstract', window );"><strong>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [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_ProfitLoss', window );">Net loss</a></td>
<td class="num">$ (89,869)<span></span>
</td>
<td class="num">$ (49,882)<span></span>
</td>
</tr>
<tr class="re">
<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 losses on debt securities, net of tax</a></td>
<td class="num">(3,006)<span></span>
</td>
<td class="num">(1,954)<span></span>
</td>
</tr>
<tr class="ro">
<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="num">(126)<span></span>
</td>
<td class="nump">9<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_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest', window );">Comprehensive loss</a></td>
<td class="num">(93,001)<span></span>
</td>
<td class="num">(51,827)<span></span>
</td>
</tr>
<tr class="ro">
<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 loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,254)<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_ComprehensiveIncomeNetOfTax', window );">Comprehensive loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">$ (93,001)<span></span>
</td>
<td class="num">$ (41,573)<span></span>
</td>
</tr>
</table>
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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 and other comprehensive income, attributable to parent entity. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
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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>
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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_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest</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 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>
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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>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>
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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, 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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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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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 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 22<br> -URI http://asc.fasb.org/extlink&amp;oid=120311839&amp;loc=d3e8736-108599<br><br>Reference 12: 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 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(1)<br> -URI 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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>
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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>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_StatementOfIncomeAndComprehensiveIncomeAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_StatementOfIncomeAndComprehensiveIncomeAbstract</td>
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<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191065018920">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th"><div>Common Stock [Member]</div></th>
<th class="th"><div>Additional Paid In Capital [Member]</div></th>
<th class="th"><div>Accumulated Other Comprehensive Loss [Member]</div></th>
<th class="th"><div>Accumulated Deficit [Member]</div></th>
<th class="th"><div>Total Ionis Stockholders' Equity [Member]</div></th>
<th class="th"><div>Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]</div></th>
<th class="th"><div>Total</div></th>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">$ 1,985,650<span></span>
</td>
<td class="num">$ (25,290)<span></span>
</td>
<td class="num">$ (596,495)<span></span>
</td>
<td class="nump">$ 1,364,005<span></span>
</td>
<td class="nump">$ 213,453<span></span>
</td>
<td class="nump">$ 1,577,458<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 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">(39,628)<span></span>
</td>
<td class="num">(39,628)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(39,628)<span></span>
</td>
</tr>
<tr class="re">
<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 losses, net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,954)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,954)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(1,954)<span></span>
</td>
</tr>
<tr class="ro">
<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">9<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">9<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">9<span></span>
</td>
</tr>
<tr class="re">
<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">$ 0<span></span>
</td>
<td class="nump">7,652<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,652<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,652<span></span>
</td>
</tr>
<tr class="ro">
<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">606<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">(90,549)<span></span>
</td>
<td class="num">(90,550)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(90,550)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="re">
<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">40,790<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">40,790<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">40,790<span></span>
</td>
</tr>
<tr class="ro">
<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">(11,603)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(11,603)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(11,603)<span></span>
</td>
</tr>
<tr class="re">
<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">(186)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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">(6,973)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(6,973)<span></span>
</td>
<td class="num">(3,281)<span></span>
</td>
<td class="num">(10,254)<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 Mar. 31, 2020</a></td>
<td class="nump">$ 139<span></span>
</td>
<td class="nump">2,015,516<span></span>
</td>
<td class="num">(27,235)<span></span>
</td>
<td class="num">(726,672)<span></span>
</td>
<td class="nump">1,261,748<span></span>
</td>
<td class="nump">210,172<span></span>
</td>
<td class="nump">1,471,920<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 Mar. 31, 2020</a></td>
<td class="nump">139,282<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">1,895,519<span></span>
</td>
<td class="num">(21,071)<span></span>
</td>
<td class="num">(1,131,306)<span></span>
</td>
<td class="nump">743,282<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">743,282<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<tr class="re">
<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 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">(89,869)<span></span>
</td>
<td class="num">(89,869)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(89,869)<span></span>
</td>
</tr>
<tr class="re">
<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 losses, net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(3,006)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(3,006)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(3,006)<span></span>
</td>
</tr>
<tr class="ro">
<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="num">(126)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(126)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(126)<span></span>
</td>
</tr>
<tr class="re">
<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">7,758<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,759<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,759<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_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">809<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">37,861<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">37,861<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">37,861<span></span>
</td>
</tr>
<tr class="ro">
<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">(15,337)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(15,337)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(15,337)<span></span>
</td>
</tr>
<tr class="re">
<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">(251)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Mar. 31, 2021</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">$ 1,925,801<span></span>
</td>
<td class="num">$ (24,203)<span></span>
</td>
<td class="num">$ (1,221,175)<span></span>
</td>
<td class="nump">$ 680,564<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 680,564<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 Mar. 31, 2021</a></td>
<td class="nump">140,924<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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_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_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_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>
<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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-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_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_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_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>
<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 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=115929471&amp;loc=d3e21930-107793<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 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: 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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>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191070766776">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Mar. 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_NetCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Operating activities:</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_ProfitLoss', window );">Net loss</a></td>
<td class="num">$ (89,869)<span></span>
</td>
<td class="num">$ (49,882)<span></span>
</td>
</tr>
<tr class="re">
<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 loss to net cash used in operating activities:</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_Depreciation', window );">Depreciation</a></td>
<td class="nump">3,917<span></span>
</td>
<td class="nump">3,233<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense', window );">Amortization of right-of-use operating lease assets</a></td>
<td class="nump">394<span></span>
</td>
<td class="nump">393<span></span>
</td>
</tr>
<tr class="ro">
<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">544<span></span>
</td>
<td class="nump">486<span></span>
</td>
</tr>
<tr class="re">
<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">4,023<span></span>
</td>
<td class="nump">1,062<span></span>
</td>
</tr>
<tr class="ro">
<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">860<span></span>
</td>
<td class="nump">647<span></span>
</td>
</tr>
<tr class="re">
<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">37,861<span></span>
</td>
<td class="nump">40,790<span></span>
</td>
</tr>
<tr class="ro">
<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 investments</a></td>
<td class="num">(13)<span></span>
</td>
<td class="num">(246)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived', window );">Non-cash losses related to patents</a></td>
<td class="nump">221<span></span>
</td>
<td class="nump">159<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxExpenseBenefit', window );">Provision for deferred income taxes</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(2,288)<span></span>
</td>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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="nump">52,807<span></span>
</td>
<td class="nump">34,429<span></span>
</td>
</tr>
<tr class="re">
<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">(234)<span></span>
</td>
<td class="num">(2,181)<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">16,481<span></span>
</td>
<td class="nump">9,532<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable', window );">Income taxes payable</a></td>
<td class="nump">2<span></span>
</td>
<td class="num">(532)<span></span>
</td>
</tr>
<tr class="ro">
<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">(9,569)<span></span>
</td>
<td class="nump">411<span></span>
</td>
</tr>
<tr class="re">
<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="num">(36,465)<span></span>
</td>
<td class="num">(20,920)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherCurrentLiabilities', window );">Accrued liabilities and other current liabilities</a></td>
<td class="num">(11,905)<span></span>
</td>
<td class="num">(3,006)<span></span>
</td>
</tr>
<tr class="re">
<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">(23,717)<span></span>
</td>
<td class="num">(19,679)<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_NetCashProvidedByUsedInOperatingActivities', window );">Net cash used in operating activities</a></td>
<td class="num">(54,662)<span></span>
</td>
<td class="num">(7,592)<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_NetCashProvidedByUsedInInvestingActivitiesAbstract', window );"><strong>Investing activities:</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_PaymentsToAcquireAvailableForSaleSecuritiesDebt', window );">Purchases of short-term investments</a></td>
<td class="num">(330,051)<span></span>
</td>
<td class="num">(544,375)<span></span>
</td>
</tr>
<tr class="re">
<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 sale of short-term investments</a></td>
<td class="nump">411,907<span></span>
</td>
<td class="nump">459,352<span></span>
</td>
</tr>
<tr class="ro">
<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">(1,772)<span></span>
</td>
<td class="num">(9,080)<span></span>
</td>
</tr>
<tr class="re">
<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">(1,228)<span></span>
</td>
<td class="num">(904)<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">78,856<span></span>
</td>
<td class="num">(95,007)<span></span>
</td>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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">7,760<span></span>
</td>
<td class="nump">7,652<span></span>
</td>
</tr>
<tr class="re">
<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">(15,337)<span></span>
</td>
<td class="num">(11,603)<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">0<span></span>
</td>
<td class="num">(90,550)<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_NetCashProvidedByUsedInFinancingActivities', window );">Net cash used in financing activities</a></td>
<td class="num">(7,577)<span></span>
</td>
<td class="num">(94,501)<span></span>
</td>
</tr>
<tr class="ro">
<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="num">(126)<span></span>
</td>
<td class="nump">8<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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect', window );">Net increase (decrease) in cash and cash equivalents</a></td>
<td class="nump">16,491<span></span>
</td>
<td class="num">(197,092)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of period</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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at end of period</a></td>
<td class="nump">414,155<span></span>
</td>
<td class="nump">486,195<span></span>
</td>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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">594<span></span>
</td>
<td class="nump">601<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxesPaid', window );">Income taxes paid</a></td>
<td class="nump">2<span></span>
</td>
<td class="nump">3<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</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">$ 1,876<span></span>
</td>
<td class="nump">$ 4,903<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<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>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfFinancingCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</tr>
<tr>
<td style="padding-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_DeferredIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Depreciation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_EffectOfExchangeRateOnCashAndCashEquivalents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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_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_IncomeTaxesPaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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.</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><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (f)<br> -URI 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_IncomeTaxesPaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInAccountsPayable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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_IncreaseDecreaseInAccruedIncomeTaxesPayable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 period in the amount due for taxes based on the reporting entity's earnings or attributable to the entity's income earning process (business presence) within a given jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="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_IncreaseDecreaseInAccruedIncomeTaxesPayable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_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_IncreaseDecreaseInOtherCurrentLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 current liabilities 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 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_IncreaseDecreaseInOtherCurrentLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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_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_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_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_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_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_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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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_ShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SupplementalCashFlowInformationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_SupplementalCashFlowInformationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191054713800">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2021</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock', window );">Basis of Presentation</a></td>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; 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;">We prepared the unaudited interim condensed consolidated financial statements for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on the same basis as the audited financial statements for the year ended </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, with the exception of our retrospective adoption of Accounting Standards Update, or ASU, 2020-06, which simplifies</span> the accounting for convertible debt instruments<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. See Note 2, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Polices</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; font-style: italic;">Convertible Debt, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for details of our adoption of this guidance. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</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;">In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;). We formed Akcea in December 2014. </span>In July 2017, Akcea completed an <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">initial public offering, or IPO, which reduced our ownership of Akcea&#8217;s common stock below </span>100 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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>We 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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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for organization, consolidation and basis of presentation of financial statements disclosure.</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 205<br> -URI http://asc.fasb.org/topic&amp;trid=2122149<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -URI http://asc.fasb.org/topic&amp;trid=2197479<br></p></div>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191062416200">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2021</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SignificantAccountingPoliciesTextBlock', window );">Significant Accounting Policies</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2.&#160; Significant Accounting Policies</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue Recognition</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="text-decoration: underline;">Our Revenue Sources</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 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 condensed 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; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue sales milestone payments and royalties we earn under our other partnerships.</div>

<div><br/></div>

<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: TEGSEDI and WAYLIVRA revenue, net</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the United States, or U.S., through the first quarter of 2021, we sold TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that took title to TEGSEDI. The 3PL was our sole customer in the U.S. The 3PL then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In Europe, through 2020, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors. In January 2021, we began commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. In April 2021, we expanded our distribution agreement with Sobi to also include commercializing TEGSEDI in North America. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative 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 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;">See <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 5, </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 collaborations with substantive changes that occurred in 2021. Additionally, see </span>Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for a summary of each of our material collaborative 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;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

<div><br/></div>

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    <td style="width: 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: left;"><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><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;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

<div><br/></div>

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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: left;"><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: 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;">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: left;"><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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<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc3bceb6a7e27452084778319a0662fd8" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the performance obligations</div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;D 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;">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.</div>

<div><br/></div>

<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>

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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><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain. For example, in the fourth quarter of 2020, we earned a $20 million milestone payment from AstraZeneca when AstraZeneca initiated a Phase 2b study for ION449, our medicine in development targeting PCSK9 to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION449 was contingent on AstraZeneca initiating a Phase 2b 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.</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; font-style: italic; font-weight: bold;">4.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Allocate the transaction price</div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Next, we allocate the transaction price to each of our performance obligations. When we have to 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. 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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may engage a third 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:</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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  <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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  <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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  <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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  <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>
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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;">A discount rate.</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 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="z166b1a85b2984e09868eb3de11ed32b6" 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>
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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;">The estimated cost of work we will perform;</div></td>
  </tr>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z540eca949f34406e894b37392f60b2e2" 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 estimated cost of work that we will contract with third parties to perform; and</div></td>
  </tr>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z0f9a86263d6b461baaa11b805dd6f7db" 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 estimated cost of API we will use.</div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</div>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z623228cb8c3f4e0d8b2e145cac1e2f5f" 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;">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>
  </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 recognize revenue in one of two 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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: 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>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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.</div>

<div><br/></div>

<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="text-decoration: underline;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</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;">Prior to our distribution agreement with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreement with Sobi we concluded that our performance obligation is to supply finished goods inventory to Sobi. This performance obligation is a series of distinct activities that are substantially the same because we transfer title using the same criteria each time we ship inventory to Sobi. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Additionally, Sobi does not generally have a right of return.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Reserves for TEGSEDI and WAYLIVRA commercial 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;">Prior to our distribution agreement with Sobi, w</span>e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were 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 reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. 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 TEGSEDI and WAYLIVRA revenue in the corresponding period. See our revenue recognition 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>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreement with Sobi, Sobi is financially responsible for any applicable reserves.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Upfront payments</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;">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 develop IONIS-FB-L<sub>Rx</sub> for the treatment of complement-mediated diseases, we received a $75 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 $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;D 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; font-style: italic;"><span style="text-decoration: underline;">Milestone payments</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 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>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the fourth quarter of 2020, we achieved a $7.5 million milestone payment from Biogen when we advanced a target under our 2018 strategic collaboration. 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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2020, we recognized $18 million in milestone payments when Biogen initiated a Phase 1/2 trial for ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy. 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.</div>

<div><br/></div>

<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="text-decoration: underline;">License fees</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 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 fourth quarter of 2020, we earned a $30 million license fee from AstraZeneca when AstraZeneca licensed ION455, an investigational medicine in development to treat nonalcoholic steatohepatitis, or NASH.</div>

<div><br/></div>

<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="text-decoration: underline;">Sublicense fees</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize 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.</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;">Amendments to 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;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z600efe615cfe4baeaf0ee2e16280295d" 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;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zce6c576ad62d45c8942d1f34819e712c" 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;">If the goods and/or services are sold at a stand-alone selling price.</div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, 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. As part of the agreement, Bayer paid us a<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> $</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, 2020&#160;<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>

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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>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6491466c797547d99935f9e949447990" 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="zd5744957b61f43afa2185c49ea11782a" 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>

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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: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis. </span></div>

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<div style="text-align: left; text-indent: -18pt; 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="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 </span><span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3">one 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="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2021, approximately 46.8 percent of our contracts receivables were from three significant customers. As of December 31, 2020, approximately 99.5 percent of our contracts receivables were from two significant customers.</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-weight: bold;">Unbilled SPINRAZA Royalties</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;">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 condensed consolidated balance sheet.</div>

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<div style="text-align: left; text-indent: -18pt; 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 condensed consolidated balance sheet.</span> During the three months ended&#160;March 31, 2021 and 2020, we recognized $26.0 million and $28.0 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="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales 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 sales. </div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 condensed 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 March 31, 2021, 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 condensed 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, 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. These observable price changes resulted in us recognizing 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 condensed consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded 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; 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 condensed 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 March 31, 2021, 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 insignificant amount of inventory write-offs for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2021 and 2020<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;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z3b9bef3aaaa04c50b422ad84f0a316c5" 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;">March 31, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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, 2020</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;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,695</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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>
  </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;">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>
  </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;">18,197</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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>
  </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;">2,096</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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>
  </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;">1,906</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,005</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>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,199</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 condensed 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. 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: justify; margin-left: 36pt; 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 condensed consolidated balance sheet and we expense them as the services are provided.</div>

<div><br/></div>

<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 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. </span>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<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; 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 we expect to realize.</div>

<div><br/></div>

<div 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.</div>

<div><br/></div>

<div 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 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. We based our determination 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 we expect this 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. We also expect 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 continue to maintain a valuation allowance against all our consolidated U.S. federal and state net deferred tax assets.</div>

<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-weight: bold;">Long-lived 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;">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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the </span>U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>

<div><br/></div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss Per Share</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the first quarter of 2021, we computed basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the period. For the first quarter of 2021, we did not have to consider Akcea results separately in our calculation because we owned 100 percent of Akcea for the entire period. Our basic net loss per share for the three months ended March 31, 2021 was $0.64.</div>

<div><br/></div>

<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 first quarter of 2020, prior to the Akcea Acquisition, we calculated our net loss for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period to determine our total net loss attributable to our common stockholders. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s net loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share is different than our net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the three months ended March 31, 2020, was calculated as follows (in thousands, except per share amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z7b5bf2df83804d43854b69383ccbe9b3" 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 solid 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended March 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; 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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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&#8217;s</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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss Per</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Share Calculation</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(as revised*)</div></td>
    <td colspan="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: 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;">Ionis&#8217; portion of Akcea&#8217;s net loss</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"><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%; padding-bottom: 2px; background-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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.42</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(32,674</div></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%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: 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"><div style="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;">(32,674</div></td>
    <td colspan="1" style="text-align: left; 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;" 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; 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%; 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;">(7,032</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><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;" 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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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"><div style="font-family: 'Times 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;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39,706</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;" 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;" 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%; 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;">139,429</div></td>
    <td 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;">Basic net loss per share</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%; 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;">(0.28</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" class="DSPFListTable" id="z890ac6907e984110a10e1f06bbbd806e" 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; 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;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three months ended&#160;March 31, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br/></div>

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  <tr>
    <td style="width: 36pt;"/>
    <td 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;">0.125 percent convertible senior notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z36c843a3550d4b3e93b2ee38a231b0da" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the 0.125 percent convertible senior notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6a7fb101db7048108b6a191da4379108" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent convertible senior notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z153e5c3b8aac48fe89e372bb8d6e7bfe" 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: left;"><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="z57a1ef50f84c4834ae36de72c9d4698e" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze058b3b556b740b1ba0eec702d6ac87b" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z52559752271c453ba9f59a49aed78045" 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: left;"><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;">Additionally as of March 31, 2021, we had warrants related to our 0.125 percent convertible senior notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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; font-style: italic;">Adoption of ASU 2020-06</div>

<div><br/></div>

<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 ASU 2020-06, which simplifies</span> the accounting for convertible debt 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. We adopted ASU 2020-06 on January 1, 2021 under the full retrospective approach, which required us to revise our prior period financial statements. This guidance impacted our accounting for outstanding convertible debt. As of March 31, 2021, we had </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> outstanding convertible notes, our </span>0.125 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> senior convertible notes, or </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes, which mature in December 2024, and our </span>1 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> senior convertible notes, or </span>1%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes, which mature in November 2021.</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 updated guidance eliminates the cash conversion accounting model we previously followed in Accounting Standard Codification, or ASC, 470-20, which required us to separate each of our convertible debt instruments at issuance into two units of accounting, a liability component, based on our nonconvertible debt borrowing rate at issuance, and an equity component. Under ASU 2020-06, we now account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. Since we adopted ASU 2020-06 using the full retrospective approach, we were required to apply the guidance to all convertible debt instruments we had outstanding as of January 1, 2019. We recomputed the basis of each convertible debt instrument as if we accounted for each as a single unit of accounting at issuance. This update included recalculating the amortization of debt issuance costs using an updated effective interest rate. As a result of adopting ASU 2020-06, we recorded a cumulative adjustment to decrease our additional paid in capital and our accumulated deficit at January 1, 2019. We have updated these financial statements to reflect the cumulative adjustment for the periods presented. We have labeled our prior period financial statements &#8220;as revised&#8221; to indicate the change required under the new accounting guidance. Below is a summary of the change in our balance sheet at December 31, 2020 and statement of operations from our first quarter 2020 under the ASC 470-20 legacy guidance compared to the new ASU 2020-06 guidance we adopted:</div>

<div><br/></div>

<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 adjustments we made to the condensed consolidated balance sheet we originally reported at December 31, 2020 to adopt ASU 2020-06 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zec17e05117e1400f90bc7141e80f65b8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">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: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293,161</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,648</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">308,809</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent convertible senior notes</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">455,719</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">84,417</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">540,136</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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in-capital</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,113,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(218,127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,895,519</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,249,368</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">118,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,131,306</div></td>
    <td colspan="1" style="text-align: left; 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><br/></div>

<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 ASU 2020-06, our revised ending balances for our 1% Notes and 0.125% Notes as of December 31, 2020 represent the principal balance of each convertible debt instrument less debt issuance costs. Additionally, because we have deferred tax assets related to our convertible debt instruments, we also adjusted these amounts as part of our adoption of ASU 2020-06. However, because we have a full valuation allowance on our deferred tax assets, there was no impact to our condensed consolidated balance sheet related to 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;">The following table summarizes the adjustments we made to the condensed consolidated statement of operations we originally reported at March 31, 2020 to adopt ASU 2020-06 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zc88c3f1e063e47dc85bc6ded89479623" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">Three Months Ended March 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: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,990</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">8,783</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,207</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income tax benefit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(61,737</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,783</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(52,954</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income tax benefit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,257</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(185</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,072</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(58,480</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(49,882</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(48,226</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39,628</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic and diluted net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.35</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.07</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.28</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>
</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;">Under ASU 2020-06, our revised interest expense is lower as we are no longer recording non-cash interest expense related to a debt discount. This decrease was partially offset by the increase in interest expense related to the amortization of debt issuance costs because we no longer allocate a portion of our debt issuance costs to stockholders&#8217; equity at issuance. Instead, the entire debt issuance costs were recorded as a contra-liability on our condensed consolidated balance sheet at issuance and we are amortizing them over the contractual term using an updated effective interest rate. Our updated effective interest rates for our 1% Notes and 0.125% Notes were 1.4 percent and 0.5 percent, 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;">The following tables summarize the adjustments we made to our condensed consolidated statements of stockholders&#8217; equity we originally reported at December 31, 2020 and 2019 to adopt ASU 2020-06 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zbd467850ae924fb5b960ceafc6f21552" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">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: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in-capital</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,113,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(218,127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,895,519</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,249,368</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">118,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders' equity</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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    <td colspan="1" style="text-align: left; 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>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z645e923d13f9452783b88b08a82563ef" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">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>
  </tr>
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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>
  <tr>
    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in-capital</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,203,778</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(218,128</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,985,650</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(707,534</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111,039</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(596,495</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders' equity</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,684,547</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(107,089</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">1,577,458</div></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;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 in December 2019, 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 condensed 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="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment Information</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. In October 2020, we acquired the remaining common stock of Akcea that we did not own and fully integrated Akcea&#8217;s operations into ours as of January 1, 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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 condensed 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. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our 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;">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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions. During the three months ended&#160;March 31, 2021 and 2020, we did not grant any stock options or RSUs to our Board of Directors. For the three months ended&#160;March 31, 2021 and 2020, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Options:</div>

<table cellpadding="0" cellspacing="0" id="zb50774a8db064a76b4654db166588143" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">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;">1.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; 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>
  </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;">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;">55.1</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;">58.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; 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="vertical-align: bottom;" 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; font-style: italic;">ESPP:</div>

<table cellpadding="0" cellspacing="0" id="z88183c7105e442c8a19d7f09035af980" 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>
  </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;">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>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; 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>
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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>
  <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;">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;">39.1</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;">47.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; 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>
  </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;">RSU&#8217;s:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. RSUs granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees for the three months ended&#160;March 31, 2021 was $62.02 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;">PRSU&#8217;s:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added performance-based restricted stock units, or PRSU, awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Under the terms of the grants, <span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"><span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"><span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd">one third</span></span></span> of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero percentto 150 percent of the target number depending on our relative TSR.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of Dr. Monia&#8217;s PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to Dr. Monia for the three months ended March 31, 2021 was $77.17 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;">The following table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2021 and 2020 (in thousands).</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>

<table cellpadding="0" cellspacing="0" id="z568b9f2af42c4a9096bdd2cc2d011e45" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;"> 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">Cost of sales</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">237</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">Research, development and patent expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,899</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,556</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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,780</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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,997</div></td>
    <td 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: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37,861</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">40,790</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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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2021, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $101.8 million, $109.6 million and $3.8 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized non-cash stock-based compensation expense for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.4 years, 1.8 years and 1.7 years, 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; 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;">As disclosed in the &#8220;Convertible Debt&#8221; policy above within this footnote, we adopted the simplified accounting for convertible debt instrument guidance (ASU 2020-06) on January 1, 2021. Refer to the section above for the impact of adoption. We do not expect any other recently issued accounting standards to have a material impact to our financial results.</div>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191070809240">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2021</div></th></tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTextBlock', window );">Investments</a></td>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3.&#160; 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 March 31, 2021:</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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    <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%; border-bottom: #000000 double 4px;" 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;">As illustrated above, at March 31, 2021, 87 percent of our available-for-sale securities had a maturity of less than two years.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We invest in available-for-sale securities</span> with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp; Poor&#8217;s, or S&amp;P, Moody&#8217;s or Fitch, respectively.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2021, we had an ownership interest of less than 20 percent in seven private companies and two public companies with which we conduct business. The privately held companies are 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 Antisense Therapeutics Ltd. and ProQR Therapeutics N.V.</div>

<div><br/></div>

<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 style="text-align: left;"><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; 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>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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>
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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>
    <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>
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    <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="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="vertical-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>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">234,290</div></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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  <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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  <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="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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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">325,335</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,108</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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;">328,198</div></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>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">96,698</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(164</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="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;">96,570</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 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;">59,030</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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"><div 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%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,515</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">34,571</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,233</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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>
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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;">6,213</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; 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;">Total securities with a maturity of more than one year</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;">521,811</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;">3,551</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;">(489</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>
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  <tr>
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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>
    <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>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: 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>
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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;">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;">(1,514</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">3,198</div></td>
    <td colspan="1" style="text-align: 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 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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,938</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;">31,000</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: 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,514</div></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;">34,198</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"><div style="text-align: left; text-indent: 27pt; 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;" 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;">1,430,181</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21,965</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,110</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,450,036</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="zff8613ae861b4a6ba5595d275d904f87" 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; text-indent: -9pt; margin-left: 9pt; 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">&#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>
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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; text-indent: -9pt; margin-left: 9pt; 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>
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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;"><span style="text-decoration: underline;">Available-for-sale securities:</span></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>
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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;">514,182</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%;" 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;">94,234</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">94,586</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 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%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,271</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">104,455</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: 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>
    <td 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;" 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;" 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;">1,025,454</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;">2,977</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;">(71</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,028,360</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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">325,079</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,941</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;">(40</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">329,980</div></td>
    <td colspan="1" style="text-align: 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: 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;">80,099</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">185</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9</div></td>
    <td colspan="1" style="text-align: left; 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;">80,275</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 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>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4</div></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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  <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>
    <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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    <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>
    <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;" 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;" 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="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"><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">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,513,770</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,577</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(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>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#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>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: 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>
  <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>
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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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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; 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;">Total equity securities included in deposits and other assets (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,062</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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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;">31,000</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 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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">&#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>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity 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"><div style="font-family: 'Times New Roman', 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;">1,533,544</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,515</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(2,821</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;">1,555,238</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="z50ea1d1bc6054ac6969b1083cf8ef6fd" 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; 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;">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="z8f50e28fedfe4eef9cf6ee5a1a7c0ccd" 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z860f6d5bdfcf49cf808f1c8cbb8e1031" 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; 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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7074f09c0aa945fc813760e477ae0131" 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; 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;">.</span></div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our investments we consider to be temporarily impaired at </span>March 31, 2021<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. 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="z8e6e3cb9e4a844ac94194614765f5afe" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><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;">Number of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; 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;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">233,665</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(321</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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%; 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;">60,681</div></td>
    <td colspan="1" style="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;">(166</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; 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;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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; 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;">52,838</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; 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;">(35</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">297</div></td>
    <td colspan="1" style="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;">76,712</div></td>
    <td colspan="1" style="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;">(47</div></td>
    <td colspan="1" style="text-align: left; 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; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">11,343</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">(27</div></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; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">414</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">435,239</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(596</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>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements<br></strong></div></th>
<th class="th" colspan="1">3 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;">4.&#160; Fair Value Measurements</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables present the major security types we held at </span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that we regularly measure and carry at fair value. As of </span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>we did not have any investments that we valued using Level 3 inputs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. 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):</span></div>

<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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">776,776</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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    <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%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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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    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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="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>
    <td colspan="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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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,343</div></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="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: 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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  </tr>
</table>

<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: 8pt;"/></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;">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>
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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>
    <td colspan="1" style="text-align: left; 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>
    <td colspan="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>
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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;">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 (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 (5)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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 (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 (3)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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. (4)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">581,653</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;">1,163,710</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>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines on our condensed consolidated balance sheet:</div>

<div><br/></div>

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  <tr>
    <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;">Included in cash and cash equivalents on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zabaf85a12041423a8a0f27cb847986b1" 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; 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 was included in cash and cash equivalents, with the difference included in short-term investments.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6f9607f6620b4bbd9672800078d88f17" 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in short-term investments.</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z77f49d1f8884459da3bd041fd3da0886" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z577adaddd59340a88de9768ca9301d05" 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;">(5)</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 condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</div></td>
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<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our 1% Notes and 0.125% Notes had a fair value of $314.6 million and $527.3 million at March 31, 2021, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191054698504">
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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">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2021</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;">5.&#160; Collaborative Arrangements and Licensing 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Below, we have included our Biogen collaboration, which is our only collaboration with substantive changes during </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2021</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">December 31, 2020</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/></div>

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

<div><br/></div>

<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;">Biogen</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing 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 March 31, 2021, we have received $2.9 billion from our Biogen 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;">During the three months ended March 31, 2021 and 2020, 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="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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31,</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;">$</div></td>
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    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18.1</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70</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>
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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 condensed consolidated balance sheet at March 31, 2021 and December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>included deferred revenue of $447.7 million and $465.8 million, respectively, related to our relationship with 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;">During the first three months of 2021, we did not have any changes to our performance obligations, transaction price or the timing in which we expect to recognize revenue under our Biogen 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;">In April 2021, we achieved a $10 million milestone payment from Biogen when Biogen advanced ION541, an investigational medicine targeting ataxin 2 to treat patients with ALS. We will achieve the next payment of $8 million if Biogen advances one of the medicines under our 2013 strategic neurology collaboration.</div>
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for collaborative arrangements in which the entity is a participant, including a) information about the nature and purpose of such arrangements; b) its rights and obligations thereunder; c) the accounting policy for collaborative arrangements; and d) the income statement classification and amounts attributable to transactions arising from the collaborative arrangement between participants.</p></div>
<a href="javascript:void(0);" onclick="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 808<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6931272&amp;loc=SL5834143-161434<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 808<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=6931272&amp;loc=SL5834143-161434<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 808<br> -URI http://asc.fasb.org/topic&amp;trid=5833765<br></p></div>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191058895752">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2021</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtDisclosureAbstract', window );"><strong>Convertible Debt [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_DebtDisclosureTextBlock', 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;">6. 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; font-style: italic;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0 Percent</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Convertible Senior Notes and Call Spread</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 April 2021, we completed a $632.5 million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the 0 percent convertible senior notes, or 0% Notes, to repurchase $247.9 million in principal of our 1% Notes for $257.0 million.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Following the closing of the debt transaction in April 2021, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes outstanding (amounts in millions except interest rate and price per share data):</div>

<div><br/></div>

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  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" 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;" 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes</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: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: top;" 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;" 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;"><span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde">April 2026</span></div></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; background-color: #CCEEFF;" 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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.84</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.39</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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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;">In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The call spread cost us $46.9 million, of which $136.7 million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0% Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not have any rights with respect to the note hedges and warrants.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">0.125 Percent Convertible Senior Notes and Call Spread</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2021, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):</div>

<div><br/></div>

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  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" 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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0.125% Notes</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" 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;" 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;"><span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec">December 2024</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.28</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">123.38</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.1</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>
</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In conjunction with the issuance of our </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes in December 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our </span>0.125% Notes by increasing the effective conversion price on our 0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We increased our effective conversion price to $</span>123.38<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> with the same number of underlying shares as our </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes. The call spread cost us $</span>52.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, of which $</span>108.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million was for the note hedge purchase, offset by $</span>56.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received for selling the warrants. Similar to our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges will expire upon maturity of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> do not have any rights with respect to the note hedges and warrants.</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount paid for the note hedges and the amount received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1 Percent Convertible Senior Notes</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2021, we had the following 1% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z18f2e28c3bf848fab4205a897b0abb11" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;" 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;" 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;"><span style="-sec-ix-hidden:Fact_cca8f6878ebf4cc88a7c1b64303ba443">November 2021</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
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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;">In April 2021, we repurchased $247.9 million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result, in April 2021, the remaining principal outstanding for our 1% Notes was $62.0 million, resulting in 0.9 million shares of common stock subject to conversion. As a result of the repurchase, we reclassified the repurchased portion of our 1% Notes from current to non-current liabilities on our condensed consolidated balance sheet as of March 31, 2021 because we replaced this portion of our outstanding debt with long-term debt.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Other Terms of Convertible Senior Notes</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The 0%, 0.125% and 1% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.</div>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Severance and Retention Costs<br></strong></div></th>
<th class="th" colspan="1">3 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;">7. Severance and Retention Costs</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;">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;">As a result of the Akcea Acquisition in October 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total estimated severance and retention expenses related to the Akcea Acquisition (in millions):</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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.5</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenses incurred in the three months ended December 31, 2020</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.3</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;">Expenses incurred in the three months ended March 31, 2021</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>
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    <td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Remaining estimated expenses to be recognized through October 2021</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;">7.8</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>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our severance and retention expenses related to the Akcea Acquisition that we recognized during the three months ended&#160;March 31, 2021 (in millions):</div>

<div><br/></div>

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    <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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2021</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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <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><br/></div>

<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 amounts related to the Akcea Acquisition that we included in accrued compensation for the period indicated (in millions):</div>

<div><br/></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: 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2021</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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: left; text-indent: 16.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts expensed during the period</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1</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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 16.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Reserve adjustments during 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;">(0.7</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net amount expensed during the period</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.4</div></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%; 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>
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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="vertical-align: bottom; width: 1%; padding-bottom: 4px;" 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;">The reserve adjustments during the period primarily related to forfeitures of severance and retention payments as a result of employee terminations before they earned the 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; font-style: italic;">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;">As a result of restructuring our European operations, or Restructured European Operations, in December 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total severance and retention expenses related to our Restructured European Operations (in millions):</div>

<div><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">&#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%; 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>
    <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="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;">0.4</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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<div><br/></div>

<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 expenses related to our Restructured European Operations that we recognized during the three months ended&#160;March 31, 2021 (in millions):</div>

<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>
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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;">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>
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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>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</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><br/></div>

<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 amounts related to our Restructured European operations that we included in accrued compensation for the periods indicated (in millions):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z29b1189fd5b24a6ca7fd9d3c5320b342" 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="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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2021</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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#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;">12.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: left; text-indent: 18.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts expensed during the period</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.2</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 colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <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: top; width: 88%;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net amount expensed during the period</div></td>
    <td colspan="1" style="vertical-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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <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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    <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;">1.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<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 reserve adjustments during the period primarily related to tax expense adjustments.</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;">Restructured North American TEGSEDI 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;">In April 2021, we entered into a distribution agreement with Sobi for TEGSEDI in North America. Under the terms of the distribution agreement, we will retain the marketing authorizations for TEGSEDI in the U.S. and Canada. We will continue to supply commercial product to Sobi and manage regulatory and manufacturing processes, as well as relationships with key opinion leaders. We will also continue to lead the TEGSEDI global commercial strategy. Sobi will otherwise have responsibility for commercializing TEGSEDI in the U.S. and Canada and will assume these activities by August 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In connection with restructuring our North American TEGSEDI operations, or Restructured North American TEGSEDI Operations, we enacted a plan to reorganize our Akcea workforce in North America to better align with the needs of our business, or the Reorganization Plan, and to focus on our wholly owned pipeline. Under the Reorganization Plan, we expect to incur restructuring charges in the range of $11 million to $14 million principally in the second quarter of 2021.</div>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basis of Presentation (Policies)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2021</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_BasisOfAccountingPolicyPolicyTextBlock', window );">Basis of Presentation</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;">We prepared the unaudited interim condensed consolidated financial statements for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on the same basis as the audited financial statements for the year ended </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, with the exception of our retrospective adoption of Accounting Standards Update, or ASU, 2020-06, which simplifies</span> the accounting for convertible debt instruments<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. See Note 2, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Polices</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; font-style: italic;">Convertible Debt, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for details of our adoption of this guidance. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</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_ConsolidationPolicyTextBlock', window );">Consolidation</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;">In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;). We formed Akcea in December 2014. </span>In July 2017, Akcea completed an <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">initial public offering, or IPO, which reduced our ownership of Akcea&#8217;s common stock below </span>100 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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>We 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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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for basis of accounting, or basis of presentation, used to prepare the financial statements (for example, US Generally Accepted Accounting Principles, Other Comprehensive Basis of Accounting, IFRS).</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>
<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 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></p></div>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191061915288">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies (Policies)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2021</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock', window );">Revenue Recognition</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-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Revenue Recognition</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="text-decoration: underline;">Our Revenue Sources</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 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 condensed 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; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue sales milestone payments and royalties we earn under our other partnerships.</div>

<div><br/></div>

<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: TEGSEDI and WAYLIVRA revenue, net</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the United States, or U.S., through the first quarter of 2021, we sold TEGSEDI through an exclusive distribution agreement with a third-party logistics company, or 3PL, that took title to TEGSEDI. The 3PL was our sole customer in the U.S. The 3PL then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In Europe, through 2020, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors. In January 2021, we began commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. In April 2021, we expanded our distribution agreement with Sobi to also include commercializing TEGSEDI in North America. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative 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 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;">See <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 5, </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 collaborations with substantive changes that occurred in 2021. Additionally, see </span>Note 6, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for a summary of each of our material collaborative 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;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z8d9a9d8d26f2470084b2214919ea76f3" 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;">1.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the contract</div></td>
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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

<div><br/></div>

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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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partner approved the contract and we are both committed to perform our obligations;</div></td>
  </tr>
</table>

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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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div></td>
  </tr>
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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>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z95ce7f6c09a443e2a4a91ca387fc7742" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe collectability of the consideration is probable.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zc3bceb6a7e27452084778319a0662fd8" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Identify the performance obligations</div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract. We typically have only one performance obligation at the inception of a contract, which is to perform R&amp;D 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;">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.</div>

<div><br/></div>

<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="z3c0093ecffd840baac4436225341455a" 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>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain. For example, in the fourth quarter of 2020, we earned a $20 million milestone payment from AstraZeneca when AstraZeneca initiated a Phase 2b study for ION449, our medicine in development targeting PCSK9 to lower LDL-cholesterol. We did not consider the milestone payment probable until AstraZeneca achieved the milestone event because advancing ION449 was contingent on AstraZeneca initiating a Phase 2b 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.</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; font-style: italic; font-weight: bold;">4.</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; 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;">Next, we allocate the transaction price to each of our performance obligations. When we have to 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. 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.</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 may engage a third 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:</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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  <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="z58e5ede32c2e40818bde215370ff85ac" 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="zb77919c030b94f00bca1adbf728104d1" 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>
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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 income taxes; 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;">A discount rate.</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 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="z166b1a85b2984e09868eb3de11ed32b6" 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>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zb9d178113c9d49599ac193e5517205cb" 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 estimated cost of work we will perform;</div></td>
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<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z540eca949f34406e894b37392f60b2e2" 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 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="z0f9a86263d6b461baaa11b805dd6f7db" 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 estimated cost of API we will use.</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;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.</div>

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

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z623228cb8c3f4e0d8b2e145cac1e2f5f" 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;">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="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize revenue in one of two 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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>

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<div style="display:none;"><br/></div>
<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="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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.</div>

<div><br/></div>

<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="text-decoration: underline;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</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;">Prior to our distribution agreement with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreement with Sobi we concluded that our performance obligation is to supply finished goods inventory to Sobi. This performance obligation is a series of distinct activities that are substantially the same because we transfer title using the same criteria each time we ship inventory to Sobi. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Additionally, Sobi does not generally have a right of return.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Reserves for TEGSEDI and WAYLIVRA commercial 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;">Prior to our distribution agreement with Sobi, w</span>e recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were 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 reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. 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 TEGSEDI and WAYLIVRA revenue in the corresponding period. See our revenue recognition 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>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales.</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreement with Sobi, Sobi is financially responsible for any applicable reserves.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Research and development revenue under collaboration agreements:</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="text-decoration: underline;">Upfront payments</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;">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 develop IONIS-FB-L<sub>Rx</sub> for the treatment of complement-mediated diseases, we received a $75 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 $75 million upfront payment using an input method over the estimated period of time we are providing R&amp;D 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; font-style: italic;"><span style="text-decoration: underline;">Milestone payments</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 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>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the fourth quarter of 2020, we achieved a $7.5 million milestone payment from Biogen when we advanced a target under our 2018 strategic collaboration. 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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2020, we recognized $18 million in milestone payments when Biogen initiated a Phase 1/2 trial for ION464, our medicine in development targeting alpha-synuclein to treat patients with multiple system atrophy. 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.</div>

<div><br/></div>

<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="text-decoration: underline;">License fees</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 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 fourth quarter of 2020, we earned a $30 million license fee from AstraZeneca when AstraZeneca licensed ION455, an investigational medicine in development to treat nonalcoholic steatohepatitis, or NASH.</div>

<div><br/></div>

<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="text-decoration: underline;">Sublicense fees</span></div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize 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.</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;">Amendments to 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;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z600efe615cfe4baeaf0ee2e16280295d" 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;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="zce6c576ad62d45c8942d1f34819e712c" 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;">If the goods and/or services are sold at a stand-alone selling price.</div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, 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. As part of the agreement, Bayer paid us a<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> $</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, 2020&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for further discussion of the Bayer collaboration.</span></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; font-weight: bold;">Multiple 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;">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="zc3bf1afbdaa6479890cee729adac381a" 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="z6491466c797547d99935f9e949447990" 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="zd5744957b61f43afa2185c49ea11782a" 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: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis. </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>
<td class="text">
<div style="display:none;"><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;">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 </span><span style="-sec-ix-hidden:Fact_cb46feec840d4d05b86df2a2af3b44c3">one quarter</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of billing our partner or customer</span>.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2021, approximately 46.8 percent of our contracts receivables were from three significant customers. As of December 31, 2020, approximately 99.5 percent of our contracts receivables were from two significant customers.</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: -18pt; 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 condensed 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: -18pt; 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 condensed consolidated balance sheet.</span> During the three months ended&#160;March 31, 2021 and 2020, we recognized $26.0 million and $28.0 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 Sales</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales 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 sales. </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="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 condensed 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 March 31, 2021, 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 condensed 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, 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. These observable price changes resulted in us recognizing 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 condensed consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.</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_InventoryPolicyTextBlock', window );">Inventory Valuation</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-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 condensed 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 March 31, 2021, 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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 insignificant amount of inventory write-offs for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2021 and 2020<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;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z3b9bef3aaaa04c50b422ad84f0a316c5" 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;">March 31, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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, 2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,695</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-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>
  </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;">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>
  </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;">18,197</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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>
  </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;">2,096</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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>
  </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;">1,906</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,005</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>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,199</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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>
  </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_LesseeLeasesPolicyTextBlock', window );">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; 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 condensed 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. 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_ResearchAndDevelopmentExpensePolicy', window );">Research and Development 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;">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 condensed consolidated balance sheet and we expense them as the services are provided.</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_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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. </span>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<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></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_IncomeTaxPolicyTextBlock', window );">Income Taxes</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-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 we expect to realize.</div>

<div><br/></div>

<div 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.</div>

<div><br/></div>

<div 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 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. We based our determination 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 we expect this 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. We also expect 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 continue to maintain a valuation allowance against all our consolidated U.S. federal and state net deferred tax assets.</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_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock', window );">Long-Lived Assets</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-weight: bold;">Long-lived 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;">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.</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_UseOfEstimates', window );">Use of Estimates</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-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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the </span>U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</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_EarningsPerSharePolicyTextBlock', window );">Basic and Diluted Net Loss per Share</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss Per Share</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the first quarter of 2021, we computed basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the period. For the first quarter of 2021, we did not have to consider Akcea results separately in our calculation because we owned 100 percent of Akcea for the entire period. Our basic net loss per share for the three months ended March 31, 2021 was $0.64.</div>

<div><br/></div>

<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 first quarter of 2020, prior to the Akcea Acquisition, we calculated our net loss for Ionis on a stand-alone basis plus our share of Akcea&#8217;s net loss for the period to determine our total net loss attributable to our common stockholders. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s net loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share is different than our net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our basic net loss per share for the three months ended March 31, 2020, was calculated as follows (in thousands, except per share amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z7b5bf2df83804d43854b69383ccbe9b3" 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 solid 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended March 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; 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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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&#8217;s</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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss Per</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Share Calculation</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(as revised*)</div></td>
    <td colspan="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: 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;">Ionis&#8217; portion of Akcea&#8217;s net loss</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"><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%; padding-bottom: 2px; background-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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.42</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(32,674</div></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%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: 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"><div style="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;">(32,674</div></td>
    <td colspan="1" style="text-align: left; 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;" 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; 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%; 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;">(7,032</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><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;" 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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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"><div style="font-family: 'Times 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;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39,706</div></td>
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  </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; 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;" 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%; 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;">139,429</div></td>
    <td 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;">Basic net loss per share</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%; 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;">(0.28</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" class="DSPFListTable" id="z890ac6907e984110a10e1f06bbbd806e" 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; 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;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three months ended&#160;March 31, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br/></div>

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  <tr>
    <td style="width: 36pt;"/>
    <td 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;">0.125 percent convertible senior notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z36c843a3550d4b3e93b2ee38a231b0da" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the 0.125 percent convertible senior notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z6a7fb101db7048108b6a191da4379108" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent convertible senior notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z153e5c3b8aac48fe89e372bb8d6e7bfe" 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: left;"><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="z57a1ef50f84c4834ae36de72c9d4698e" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="ze058b3b556b740b1ba0eec702d6ac87b" 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: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z52559752271c453ba9f59a49aed78045" 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: left;"><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;">Additionally as of March 31, 2021, we had warrants related to our 0.125 percent convertible senior notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>
<span></span>
</td>
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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_DebtPolicyTextBlock', window );">Convertible Debt</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-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; font-style: italic;">Adoption of ASU 2020-06</div>

<div><br/></div>

<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 ASU 2020-06, which simplifies</span> the accounting for convertible debt 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. We adopted ASU 2020-06 on January 1, 2021 under the full retrospective approach, which required us to revise our prior period financial statements. This guidance impacted our accounting for outstanding convertible debt. As of March 31, 2021, we had </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> outstanding convertible notes, our </span>0.125 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> senior convertible notes, or </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes, which mature in December 2024, and our </span>1 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> senior convertible notes, or </span>1%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes, which mature in November 2021.</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 updated guidance eliminates the cash conversion accounting model we previously followed in Accounting Standard Codification, or ASC, 470-20, which required us to separate each of our convertible debt instruments at issuance into two units of accounting, a liability component, based on our nonconvertible debt borrowing rate at issuance, and an equity component. Under ASU 2020-06, we now account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. Since we adopted ASU 2020-06 using the full retrospective approach, we were required to apply the guidance to all convertible debt instruments we had outstanding as of January 1, 2019. We recomputed the basis of each convertible debt instrument as if we accounted for each as a single unit of accounting at issuance. This update included recalculating the amortization of debt issuance costs using an updated effective interest rate. As a result of adopting ASU 2020-06, we recorded a cumulative adjustment to decrease our additional paid in capital and our accumulated deficit at January 1, 2019. We have updated these financial statements to reflect the cumulative adjustment for the periods presented. We have labeled our prior period financial statements &#8220;as revised&#8221; to indicate the change required under the new accounting guidance. Below is a summary of the change in our balance sheet at December 31, 2020 and statement of operations from our first quarter 2020 under the ASC 470-20 legacy guidance compared to the new ASU 2020-06 guidance we adopted:</div>

<div><br/></div>

<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 adjustments we made to the condensed consolidated balance sheet we originally reported at December 31, 2020 to adopt ASU 2020-06 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zec17e05117e1400f90bc7141e80f65b8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">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: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293,161</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,648</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">308,809</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent convertible senior notes</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">455,719</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">84,417</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">540,136</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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in-capital</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,113,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(218,127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,895,519</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,249,368</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">118,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,131,306</div></td>
    <td colspan="1" style="text-align: left; 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><br/></div>

<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 ASU 2020-06, our revised ending balances for our 1% Notes and 0.125% Notes as of December 31, 2020 represent the principal balance of each convertible debt instrument less debt issuance costs. Additionally, because we have deferred tax assets related to our convertible debt instruments, we also adjusted these amounts as part of our adoption of ASU 2020-06. However, because we have a full valuation allowance on our deferred tax assets, there was no impact to our condensed consolidated balance sheet related to 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;">The following table summarizes the adjustments we made to the condensed consolidated statement of operations we originally reported at March 31, 2020 to adopt ASU 2020-06 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zc88c3f1e063e47dc85bc6ded89479623" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">Three Months Ended March 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: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,990</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">8,783</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,207</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income tax benefit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(61,737</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,783</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(52,954</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income tax benefit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,257</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(185</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,072</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(58,480</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(49,882</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(48,226</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39,628</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic and diluted net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.35</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.07</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.28</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>
</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;">Under ASU 2020-06, our revised interest expense is lower as we are no longer recording non-cash interest expense related to a debt discount. This decrease was partially offset by the increase in interest expense related to the amortization of debt issuance costs because we no longer allocate a portion of our debt issuance costs to stockholders&#8217; equity at issuance. Instead, the entire debt issuance costs were recorded as a contra-liability on our condensed consolidated balance sheet at issuance and we are amortizing them over the contractual term using an updated effective interest rate. Our updated effective interest rates for our 1% Notes and 0.125% Notes were 1.4 percent and 0.5 percent, 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;">The following tables summarize the adjustments we made to our condensed consolidated statements of stockholders&#8217; equity we originally reported at December 31, 2020 and 2019 to adopt ASU 2020-06 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zbd467850ae924fb5b960ceafc6f21552" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">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: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in-capital</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,113,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(218,127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,895,519</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,249,368</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">118,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,131,306</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders' equity</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">843,347</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(100,065</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">743,282</div></td>
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  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z645e923d13f9452783b88b08a82563ef" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">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>
  </tr>
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in-capital</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,203,778</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(218,128</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,985,650</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(707,534</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111,039</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(596,495</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders' equity</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,684,547</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(107,089</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">1,577,458</div></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_DerivativesPolicyTextBlock', window );">Call Spread</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-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 in December 2019, 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 condensed 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>
</tr>
<tr class="ro">
<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>
<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-weight: bold;">Segment Information</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. In October 2020, we acquired the remaining common stock of Akcea that we did not own and fully integrated Akcea&#8217;s operations into ours as of January 1, 2021.</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_ShareBasedCompensationOptionAndIncentivePlansPolicy', 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; 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 condensed 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. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our 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;">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.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions. During the three months ended&#160;March 31, 2021 and 2020, we did not grant any stock options or RSUs to our Board of Directors. For the three months ended&#160;March 31, 2021 and 2020, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Options:</div>

<table cellpadding="0" cellspacing="0" id="zb50774a8db064a76b4654db166588143" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">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>
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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: 76%;" valign="bottom"><div style="text-align: left; 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>
  </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;">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>
  </tr>
  <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"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7 years</div></td>
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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; font-style: italic;">ESPP:</div>

<table cellpadding="0" cellspacing="0" id="z88183c7105e442c8a19d7f09035af980" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">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: 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;">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;">0.1</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>
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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: 76%;" valign="bottom"><div style="text-align: left; 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>
  </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;">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;">39.1</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;">47.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; 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>
  </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;">RSU&#8217;s:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. RSUs granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees for the three months ended&#160;March 31, 2021 was $62.02 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;">PRSU&#8217;s:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added performance-based restricted stock units, or PRSU, awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Under the terms of the grants, <span style="-sec-ix-hidden:Fact_3ea144f70898401099a1731ad0c7e39f"><span style="-sec-ix-hidden:Fact_b531c97d5a394e3f8a5454ecd82ddb93"><span style="-sec-ix-hidden:Fact_b2b6dbe875764e78b9cce0b8464216dd">one third</span></span></span> of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero percentto 150 percent of the target number depending on our relative TSR.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of Dr. Monia&#8217;s PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to Dr. Monia for the three months ended March 31, 2021 was $77.17 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;">The following table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2021 and 2020 (in thousands).</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>

<table cellpadding="0" cellspacing="0" id="z568b9f2af42c4a9096bdd2cc2d011e45" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;"> 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">Cost of sales</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">237</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">Research, development and patent expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,899</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,556</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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,780</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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,997</div></td>
    <td 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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</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;" 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;">40,790</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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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2021, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $101.8 million, $109.6 million and $3.8 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized non-cash stock-based compensation expense for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.4 years, 1.8 years and 1.7 years, respectively.</div>
<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Impact of Recently Issued Accounting Standards</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; 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;">As disclosed in the &#8220;Convertible Debt&#8221; policy above within this footnote, we adopted the simplified accounting for convertible debt instrument guidance (ASU 2020-06) on January 1, 2021. Refer to the section above for the impact of adoption. We do not expect any other recently issued accounting standards to have a material impact to our financial results.</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>
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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>
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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>
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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>
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<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>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IntangibleAssetsFiniteLivedPolicy</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</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_InventoryPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</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_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>
<td>us-gaap_</td>
</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_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>
<td>us-gaap_</td>
</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_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>
<td>us-gaap_</td>
</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_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>
<td>us-gaap_</td>
</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_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>
<td>us-gaap_</td>
</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_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>
<td>us-gaap_</td>
</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_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>
<td>us-gaap_</td>
</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>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingPolicyPolicyTextBlock</td>
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<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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<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">
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<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;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191054623800">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,199</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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>
  </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_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock', window );">Basic Net Loss 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;">Our basic net loss per share for the three months ended March 31, 2020, was calculated as follows (in thousands, except per share amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z7b5bf2df83804d43854b69383ccbe9b3" 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 solid 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three months ended March 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; 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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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&#8217;s</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;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss Per</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Share Calculation</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(as revised*)</div></td>
    <td colspan="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: 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;">Ionis&#8217; portion of Akcea&#8217;s net loss</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"><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%; padding-bottom: 2px; background-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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.42</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(32,674</div></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%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: 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"><div style="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;">(32,674</div></td>
    <td colspan="1" style="text-align: left; 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;" 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; 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%; 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;">(7,032</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><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;" 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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <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"><div style="font-family: 'Times 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;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39,706</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;" 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;" 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%; 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;">139,429</div></td>
    <td 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;">Basic net loss per share</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%; 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;">(0.28</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" class="DSPFListTable" id="z890ac6907e984110a10e1f06bbbd806e" 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; 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;">We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for further information.</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_ScheduleOfNewAccountingPronouncementsAndChangesInAccountingPrinciplesTextBlock', window );">Adoption of ASU 2020-06</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 adjustments we made to the condensed consolidated balance sheet we originally reported at December 31, 2020 to adopt ASU 2020-06 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zec17e05117e1400f90bc7141e80f65b8" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">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: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">293,161</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,648</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent convertible senior notes</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">455,719</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">84,417</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">540,136</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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in-capital</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,113,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(218,127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,895,519</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,249,368</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">118,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,131,306</div></td>
    <td colspan="1" style="text-align: left; 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><br/></div>

<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 adjustments we made to the condensed consolidated statement of operations we originally reported at March 31, 2020 to adopt ASU 2020-06 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zc88c3f1e063e47dc85bc6ded89479623" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">Three Months Ended March 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: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,990</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">8,783</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,207</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income tax benefit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(61,737</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,783</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(52,954</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income tax benefit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,257</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(185</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,072</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(58,480</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(49,882</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(48,226</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,598</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(39,628</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic and diluted net loss per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.35</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.07</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.28</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>
</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 tables summarize the adjustments we made to our condensed consolidated statements of stockholders&#8217; equity we originally reported at December 31, 2020 and 2019 to adopt ASU 2020-06 (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zbd467850ae924fb5b960ceafc6f21552" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">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: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in-capital</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,113,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(218,127</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,895,519</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,249,368</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">118,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(1,131,306</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders' equity</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">843,347</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(100,065</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">743,282</div></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>

<table cellpadding="0" cellspacing="0" id="z645e923d13f9452783b88b08a82563ef" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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: 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;">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>
  </tr>
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Previously</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Reported</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASU 2020-06</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Adjustment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">As Revised</div></td>
    <td colspan="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;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in-capital</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,203,778</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(218,128</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,985,650</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 64%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(707,534</div></td>
    <td colspan="1" style="text-align: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111,039</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(596,495</div></td>
    <td colspan="1" style="text-align: left; 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%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders' equity</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,684,547</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(107,089</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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;">1,577,458</div></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_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</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;">Employee Stock Options:</div>

<table cellpadding="0" cellspacing="0" id="zb50774a8db064a76b4654db166588143" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">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;">1.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: left; 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>
  </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;">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;">55.1</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;">58.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; 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;">4.9 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="ro">
<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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ESPP:</div>

<table cellpadding="0" cellspacing="0" id="z88183c7105e442c8a19d7f09035af980" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">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;">0.1</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;">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>
  </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;">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>
  </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;">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;">39.1</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;">47.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; 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>
  </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_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 three months ended&#160;March 31, 2021 and 2020 (in thousands).</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>

<table cellpadding="0" cellspacing="0" id="z568b9f2af42c4a9096bdd2cc2d011e45" 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;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;"> 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">Cost of sales</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">237</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </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;">Research, development and patent expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,899</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,556</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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expense</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,780</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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,997</div></td>
    <td 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: left; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37,861</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">40,790</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>
</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_AccountingPoliciesAbstract</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>
<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_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock">
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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the effect of income (loss) on basic earnings per share.</p></div>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191056183848">
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<th class="th" colspan="1">3 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 contract maturity of the available-for-sale securities we held as of March 31, 2021:</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 following is a summary of our investments (in thousands):</div>

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

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    <td 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>
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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"><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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">80,703</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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>
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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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">80,993</div></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;">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;">234,164</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">126</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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: 52%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">121,776</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">220</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">121,974</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;">5,137</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">&#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;">5,130</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; 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;">Total securities with a maturity of one year or less</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;">888,596</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;">2,476</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;">(107</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>
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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;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">325,335</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #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;">328,198</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" 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;">96,698</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" 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="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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
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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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    <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;">6,213</div></td>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; 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;">Total securities with a maturity of more than one year</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;">521,811</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>
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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"><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;">524,873</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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,410,407</div></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>
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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;">(596</div></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>
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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>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#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>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: 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>
  <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>
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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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  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; 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;">Total equity securities included in deposits and other assets (4)</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="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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  </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">&#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>
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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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  </tr>
  <tr>
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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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    <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"><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>
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  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="zff8613ae861b4a6ba5595d275d904f87" 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; text-indent: -9pt; margin-left: 9pt; 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">&#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>
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  </tr>
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; 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>
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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;"><span style="text-decoration: underline;">Available-for-sale securities:</span></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%;" 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;">94,234</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">94,586</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 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%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,271</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">104,455</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: 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>
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  <tr>
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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</div></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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  <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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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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  <tr>
    <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>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div 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>
    <td colspan="1" style="text-align: 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: 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31,779</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">31,854</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div 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>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; 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;">Total securities with a maturity of more than one year</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;">488,316</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;">5,600</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;">(69</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;">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: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,513,770</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(140</div></td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
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  </tr>
  <tr>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: 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>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: 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: 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;" 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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,062</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,938</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;">31,000</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: 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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;" valign="bottom"><div style="text-align: left; text-indent: 27pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity 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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,533,544</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,515</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,821</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,555,238</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="z50ea1d1bc6054ac6969b1083cf8ef6fd" 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; 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;">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="z8f50e28fedfe4eef9cf6ee5a1a7c0ccd" 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z860f6d5bdfcf49cf808f1c8cbb8e1031" 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; 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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" id="z7074f09c0aa945fc813760e477ae0131" 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; 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;">.</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 following is a summary of our investments we consider to be temporarily impaired at </span>March 31, 2021<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. 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="z8e6e3cb9e4a844ac94194614765f5afe" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><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;">Number of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; 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;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">233,665</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(321</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191054798184">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2021</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following tables present the major security types we held at </span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that we regularly measure and carry at fair value. As of </span>March 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>December 31, 2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>we did not have any investments that we valued using Level 3 inputs<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. 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):</span></div>

<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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  <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; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">776,776</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;">Debt securities issued by U.S. government agencies (3)</div></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="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>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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: 64%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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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>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">156,545</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 64%;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (3)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,343</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">11,343</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. (4)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,198</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,198</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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>
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  <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>
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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>
    <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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<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z8fa75e640870498fb69868b78d69ca2a" 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>
    <td colspan="1" style="vertical-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>
    <td colspan="1" style="vertical-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 (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
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<div><br/></div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines on our condensed consolidated balance sheet:</div>

<div><br/></div>

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<div><br/></div>

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<div><br/></div>

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<div><br/></div>

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<div><br/></div>

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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 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;">During the three months ended March 31, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191062196872">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2021</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;">Following the closing of the debt transaction in April 2021, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes outstanding (amounts in millions except interest rate and price per share data):</div>

<div><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;">632.5</div></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;">57.84</div></td>
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    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
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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;">76.39</div></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;">10.9</div></td>
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<td class="text">&#160;<span></span>
</td>
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</td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2021, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):</div>

<div><br/></div>

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    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
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<td class="text">&#160;<span></span>
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<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2021, we had the following 1% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):</div>

<div><br/></div>

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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;">0.8</div></td>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191056121256">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Severance and Retention Costs (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2021</div></th></tr>
<tr class="rh">
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<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_SeveranceAndRetentionCostsLineItems', window );"><strong>Severance and Retention Costs [Abstract]</strong></a></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a result of the Akcea Acquisition in October 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total estimated severance and retention expenses related to the Akcea Acquisition (in millions):</div>

<div><br/></div>

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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;">Expenses incurred in the three months ended December 31, 2020</div></td>
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  <tr>
    <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;">Expenses incurred in the three months ended March 31, 2021</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;">5.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Remaining estimated expenses to be recognized through October 2021</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;">7.8</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>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our severance and retention expenses related to the Akcea Acquisition that we recognized during the three months ended&#160;March 31, 2021 (in millions):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z66701bad96c440b099dd3e06c59b7285" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">5.4</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the severance and retention reserve amounts related to the Akcea Acquisition that we included in accrued compensation for the period indicated (in millions):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z5b489fcb281c4c45bd3bb47f2580dae7" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">Beginning balance</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;">14.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: left; text-indent: 16.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts expensed during the period</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.1</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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: 16.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Reserve adjustments during 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;">(0.7</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: top; width: 88%;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net amount expensed during the period</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.4</div></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%; 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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9.0</div></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: 88%; padding-bottom: 4px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_RestructuredEuropeanOperationsMember', window );">Restructured European Operations [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_SeveranceAndRetentionCostsLineItems', window );"><strong>Severance and Retention Costs [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_ScheduleOfRestructuringAndRelatedCostsTextBlock', window );">Severance and Retention Costs</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 a result of restructuring our European operations, or Restructured European Operations, in December 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total severance and retention expenses related to our Restructured European Operations (in millions):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z4017ce63a44d40988c5306fc8d86c8e2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Severance and Retention Expenses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total estimated 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;">13.6</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: top; width: 88%;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenses incurred in the three months ended December 31, 2020</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.5</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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenses incurred in the three months ended March 31, 2021</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; padding-bottom: 4px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Remaining estimated expenses through October 2021</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;">0.4</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>

<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 expenses related to our Restructured European Operations that we recognized during the three months ended&#160;March 31, 2021 (in millions):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z88d9ea5d72574713a598d1c5c92f65ca" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expenses</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">0.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the severance and retention reserve amounts related to our Restructured European operations that we included in accrued compensation for the periods indicated (in millions):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" id="z29b1189fd5b24a6ca7fd9d3c5320b342" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
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<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">$ 111,607<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 133,367<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_MajorCustomersAxis=ions_BiogenIncMember', 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>
</tr>
<tr class="re">
<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>
</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="nump">2<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInJuly2015WithAstrazenecaMember', window );">AstraZeneca [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>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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">$ 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="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>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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">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 );">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>
</tr>
<tr class="ro">
<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>
</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="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>
</tr>
<tr class="re">
<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>
</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_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="nump">$ 7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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] | 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>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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">$ 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>
</tr>
<tr 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>
</tr>
<tr class="re">
<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>
</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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
</tr>
<tr class="ro">
<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>
</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>
</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>
</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>
</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_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_Ion449Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_Ion449Member</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>
</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_us-gaap_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInApril2018WithBiogenMember</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</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_Ion464Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_Ion464Member</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>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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInMay2015WithBayerMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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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_TypeOfArrangementAxis=ions_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementAmendedInFebruary2017WithBayerMember</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>37
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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">
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</head>
<body>
<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191054528616">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Contracts Receivable (Details) - Partner<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ContractReceivablesAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_NumberOfSignificantCustomers', window );">Number of significant customers</a></td>
<td class="nump">3<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember', window );">Contracts Receivables [Member] | Credit Concentration [Member] | Three Significant Customers [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">46.80%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember', window );">Contracts Receivables [Member] | Credit Concentration [Member] | Two Significant Customers [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 " 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">99.50%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfSignificantCustomers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 significant customers with which the Company does business.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfSignificantCustomers</td>
</tr>
<tr>
<td style="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_PeriodAfterBillingWhenPaymentIsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<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_SignificantPartnersAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_SignificantPartnersAbstract</td>
</tr>
<tr>
<td style="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_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_ContractReceivablesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ContractReceivablesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CreditConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_ThreeSignificantCustomersMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ThreeSignificantCustomersMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_TwoSignificantCustomersMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_TwoSignificantCustomersMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>38
<FILENAME>R26.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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<body>
<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191057762360">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Deferred Revenue (Details) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Mar. 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_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">$ 26.0<span></span>
</td>
<td class="nump">$ 28.0<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_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">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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>
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</TEXT>
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<SEQUENCE>39
<FILENAME>R27.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191061970216">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">3 Months Ended</th>
<th class="th" colspan="1">9 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Jun. 30, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </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_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>
</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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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="text">&#160;<span></span>
</td>
<td class="nump">3<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">Gain on investment</a></td>
<td class="nump">$ 13<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 246<span></span>
</td>
<td class="text">&#160;<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 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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>
</tr>
<tr 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>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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">3,000<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_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>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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">$ 5,500<span></span>
</td>
<td class="text">&#160;<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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</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>
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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 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>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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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<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>
</tr>
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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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<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_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>
<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_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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=ions_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>
</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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<DOCUMENT>
<TYPE>XML
<SEQUENCE>40
<FILENAME>R28.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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<body>
<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191073362232">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Inventory Valuation (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</tr>
<tr class="ro">
<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">$ 18,197<span></span>
</td>
<td class="nump">$ 16,708<span></span>
</td>
</tr>
<tr class="re">
<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">2,096<span></span>
</td>
<td class="nump">2,252<span></span>
</td>
</tr>
<tr class="ro">
<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">1,906<span></span>
</td>
<td class="nump">3,005<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_InventoryNet', window );">Total inventory</a></td>
<td class="nump">22,199<span></span>
</td>
<td class="nump">21,965<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_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember', window );">Clinical [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</tr>
<tr class="ro">
<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">10,695<span></span>
</td>
<td class="nump">9,206<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_CommercialRawMaterialsMember', window );">Commercial [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</tr>
<tr class="re">
<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">$ 7,502<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_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</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_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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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:monetaryItemType</td>
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<td>instant</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryNetAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_InventoryNetAbstract</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_InventoryRawMaterials">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryWorkInProcess">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:monetaryItemType</td>
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<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>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember</td>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191058864984">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details) - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Mar. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 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_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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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_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="num">$ (0.64)<span></span>
</td>
<td class="num">$ (0.28)<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="re">
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<td class="num">$ (89,869)<span></span>
</td>
<td class="num">$ (39,628)<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_NetIncomeLossAvailableToCommonStockholdersBasic', window );">Net income (loss) available to Ionis common shareholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (39,706)<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_WeightedAverageNumberOfSharesOutstandingBasic', window );">Weighted average shares outstanding (in shares)</a></td>
<td class="nump">140,770<span></span>
</td>
<td class="nump">139,429<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_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>
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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_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
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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_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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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>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
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<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
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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_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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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_NetIncomeLoss', window );">Net loss</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (7,032)<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_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>
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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_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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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>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (32,674)<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_srt_OwnershipAxis=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="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 Loss per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_WeightedAverageNumberOfSharesOwnedInSubsidiary', window );">Weighted average shares owned in Akcea (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">77,095<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 loss per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (0.42)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 loss</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (32,674)<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_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_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_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_EarningsPerShareBasicAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_EarningsPerShareBasicAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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_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>
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<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>
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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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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140190981936664">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Convertible Debt (Details)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
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<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($) </div>
<div>Note </div>
<div>$ / shares</div>
</th>
<th class="th">
<div>Mar. 31, 2020 </div>
<div>USD ($) </div>
<div>$ / shares</div>
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<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
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<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</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="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [Abstract]</strong></a></td>
<td class="text">&#160;<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_ConvertibleDebtCurrent', window );">1 percent convertible senior notes, net</a></td>
<td class="nump">$ 61,816<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 308,809<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">1,925,801<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">1,895,519<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_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="num">(1,221,175)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1,131,306)<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_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [Abstract]</strong></a></td>
<td class="text">&#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="num">(2,414)<span></span>
</td>
<td class="num">$ (2,207)<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="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesMinorityInterestAndIncomeLossFromEquityMethodInvestments', window );">Loss before income tax (expense) benefit</a></td>
<td class="num">(89,739)<span></span>
</td>
<td class="num">(52,954)<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_IncomeTaxExpenseBenefit', window );">Income tax (expense) benefit</a></td>
<td class="num">(130)<span></span>
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<td class="nump">3,072<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="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 loss</a></td>
<td class="num">(89,869)<span></span>
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<td class="num">(49,882)<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="num">$ (89,869)<span></span>
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<td class="num">$ (39,628)<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="num">$ (0.64)<span></span>
</td>
<td class="num">$ (0.28)<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="num">$ (0.64)<span></span>
</td>
<td class="num">$ (0.28)<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_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#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_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance</a></td>
<td class="nump">$ 680,564<span></span>
</td>
<td class="nump">$ 1,471,920<span></span>
</td>
<td class="nump">743,282<span></span>
</td>
<td class="nump">$ 1,577,458<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_AdditionalPaidInCapitalMember', window );">Additional Paid In Capital [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="nump">1,925,801<span></span>
</td>
<td class="nump">2,015,516<span></span>
</td>
<td class="nump">1,895,519<span></span>
</td>
<td class="nump">1,985,650<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_RetainedEarningsMember', window );">Accumulated Deficit [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">(89,869)<span></span>
</td>
<td class="num">(39,628)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="num">(1,221,175)<span></span>
</td>
<td class="num">(726,672)<span></span>
</td>
<td class="num">(1,131,306)<span></span>
</td>
<td class="num">(596,495)<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_ParentMember', window );">Total Ionis Stockholders' Equity [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">(89,869)<span></span>
</td>
<td class="num">(39,628)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="nump">$ 680,564<span></span>
</td>
<td class="nump">1,261,748<span></span>
</td>
<td class="nump">$ 743,282<span></span>
</td>
<td class="nump">1,364,005<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="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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">$ 540,679<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 540,136<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">0.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">$ 247,292<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="nump">1.40%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_RestatementAxis=srt_ScenarioPreviouslyReportedMember', window );">As Previously Reported [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">293,161<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,113,646<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1,249,368)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="num">(10,990)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 );">Loss before income tax (expense) benefit</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(61,737)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 (expense) benefit</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,257<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 loss</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(58,480)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (48,226)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 loss per share (in dollars per share) | $ / shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (0.35)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net loss per share (in dollars per share) | $ / shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (0.35)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">843,347<span></span>
</td>
<td class="nump">1,684,547<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_RestatementAxis=srt_ScenarioPreviouslyReportedMember', window );">As Previously Reported [Member] | Additional Paid In Capital [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,113,646<span></span>
</td>
<td class="nump">2,203,778<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_RestatementAxis=srt_ScenarioPreviouslyReportedMember', window );">As Previously Reported [Member] | Accumulated Deficit [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1,249,368)<span></span>
</td>
<td class="num">(707,534)<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_RestatementAxis=srt_ScenarioPreviouslyReportedMember', window );">As Previously Reported [Member] | 0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">455,719<span></span>
</td>
<td class="text">&#160;<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_RestatementAxis=srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember', window );">Adjustment [Member] | ASU 2020-06 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15,648<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(218,127)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">118,062<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 );">Net deferred tax assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeStatementAbstract', window );"><strong>Condensed Consolidated Statement of Operations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="nump">$ 8,783<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 );">Loss before income tax (expense) benefit</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">8,783<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 (expense) benefit</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(185)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 loss</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">8,598<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8,598<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 loss per share (in dollars per share) | $ / shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0.07<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 loss per share (in dollars per share) | $ / shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0.07<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(100,065)<span></span>
</td>
<td class="num">(107,089)<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_RestatementAxis=srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember', window );">Adjustment [Member] | ASU 2020-06 [Member] | Additional Paid In Capital [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(218,127)<span></span>
</td>
<td class="num">(218,128)<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_RestatementAxis=srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember', window );">Adjustment [Member] | ASU 2020-06 [Member] | Accumulated Deficit [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfStockholdersEquityAbstract', window );"><strong>Condensed Consolidated Statements of Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">118,062<span></span>
</td>
<td class="nump">$ 111,039<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_RestatementAxis=srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember', window );">Adjustment [Member] | ASU 2020-06 [Member] | 0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StatementOfFinancialPositionAbstract', window );"><strong>Condensed Consolidated Balance Sheet [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 84,417<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_DebtInstrumentNumberOfConvertibleNotes">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 outstanding 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>
<td style="white-space:nowrap;">ions_DebtInstrumentNumberOfConvertibleNotes</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_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_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_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_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_IncomeStatementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_IncomeStatementAbstract</td>
</tr>
<tr>
<td style="padding-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_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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</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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-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_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>
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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_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>
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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_RetainedEarningsAccumulatedDeficit</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> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</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_StatementOfFinancialPositionAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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</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 );">- 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_StatementOfStockholdersEquityAbstract</td>
</tr>
<tr>
<td style="padding-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_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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
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<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_StatementEquityComponentsAxis=us-gaap_AdditionalPaidInCapitalMember</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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<tr>
<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>
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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_StatementEquityComponentsAxis=us-gaap_RetainedEarningsMember</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>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="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_StatementEquityComponentsAxis=us-gaap_ParentMember</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_ConvertibleSeniorNotes0125PercentMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_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">
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<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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">
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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_RestatementAxis=srt_RevisionOfPriorPeriodAccountingStandardsUpdateAdjustmentMember</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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<head>
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<link rel="stylesheet" type="text/css" href="report.css">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Segment Information (Details)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<td class="text">&#160;<span></span>
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<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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<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>
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<TYPE>XML
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<FILENAME>R32.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;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191058729160">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Stock-Based Compensation Expense (Details)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($) </div>
<div>Period </div>
<div>$ / shares </div>
<div>shares</div>
</th>
<th class="th">
<div>Mar. 31, 2020 </div>
<div>USD ($) </div>
<div>shares</div>
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</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 37,861<span></span>
</td>
<td class="nump">$ 40,790<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_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember', window );">Cost of Sales [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 Expense [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_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">182<span></span>
</td>
<td class="nump">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_us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentExpenseMember', window );">Research, Development and Patent Expense [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_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [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_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">25,899<span></span>
</td>
<td class="nump">25,556<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_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember', window );">Selling, General and Administrative Expense [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_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [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_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">11,780<span></span>
</td>
<td class="nump">$ 14,997<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>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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 expense related to non-vested stock options</a></td>
<td class="nump">$ 101,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 4 months 24 days<span></span>
</td>
<td class="text">&#160;<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] | Board of Directors [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward', window );"><strong>Stock-based Compensation Expense [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross', window );">Stock options granted (in shares) | shares</a></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_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Stock Options [Member] | Employees [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">0.50%<span></span>
</td>
<td class="nump">1.60%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</tr>
<tr class="re">
<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">55.10%<span></span>
</td>
<td class="nump">58.90%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">4 years 10 months 24 days<span></span>
</td>
<td class="text">4 years 8 months 12 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=us-gaap_EmployeeStockMember', window );">ESPP [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">0.10%<span></span>
</td>
<td class="nump">1.10%<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></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">39.10%<span></span>
</td>
<td class="nump">47.20%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</tr>
<tr 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>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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 units</a></td>
<td class="nump">$ 109,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">1 year 9 months 18 days<span></span>
</td>
<td class="text">&#160;<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] | Board of Directors [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward', window );"><strong>Stock-based Compensation Expense [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod', window );">Units granted (in shares) | shares</a></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_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 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_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<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] | Employees [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 grant date fair value (in dollars per share) | $ / shares</a></td>
<td class="nump">$ 62.02<span></span>
</td>
<td class="text">&#160;<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_PerformanceSharesMember', window );">PRSUs [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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="nump">$ 3,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 8 months 12 days<span></span>
</td>
<td class="text">&#160;<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_PerformanceSharesMember', window );">PRSUs [Member] | Chief Executive Officer, Dr. Brett Monia [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods', window );">Number of performance periods | Period</a></td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">3 years<span></span>
</td>
<td class="text">&#160;<span></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_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest', window );">Number of units guaranteed to vest | shares</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share) | $ / shares</a></td>
<td class="nump">$ 77.17<span></span>
</td>
<td class="text">&#160;<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_PerformanceSharesMember', window );">PRSUs [Member] | Chief Executive Officer, Dr. Brett Monia [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="nump">150.00%<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_PerformanceSharesMember', window );">PRSUs [Member] | Chief Executive Officer, Dr. Brett Monia [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Chief Executive Officer, Dr. Brett Monia [Member] | One-Year Period [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<span></span>
</td>
<td class="text">&#160;<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_PerformanceSharesMember', window );">PRSUs [Member] | Chief Executive Officer, Dr. Brett Monia [Member] | Two-Year Period [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<span></span>
</td>
<td class="text">&#160;<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_PerformanceSharesMember', window );">PRSUs [Member] | Chief Executive Officer, Dr. Brett Monia [Member] | Three-Year Period [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 separate performance periods 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;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 units guaranteed to vest 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;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 units guaranteed to vest 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;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>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_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_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_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_ShareBasedCompensationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ShareBasedCompensationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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_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>
</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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</tr>
<tr>
<td style="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_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_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_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_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</tr>
<tr>
<td style="padding-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_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>
</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_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentExpenseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ResearchDevelopmentAndPatentExpenseMember</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_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>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_EmployeeStockOptionMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=ions_ShareBasedPaymentArrangementBoardOfDirectorMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_GranteeStatusAxis=ions_ShareBasedPaymentArrangementBoardOfDirectorMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=us-gaap_ShareBasedPaymentArrangementEmployeeMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_GranteeStatusAxis=us-gaap_ShareBasedPaymentArrangementEmployeeMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_EmployeeStockMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</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_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_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_AwardTypeAxis=us-gaap_PerformanceSharesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_PerformanceSharesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=srt_ChiefExecutiveOfficerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_GranteeStatusAxis=srt_ChiefExecutiveOfficerMember</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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<tr>
<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
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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>
</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_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheTwoMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ShareBasedCompensationAwardTrancheTwoMember</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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheThreeMember</td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>45
<FILENAME>R33.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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<body>
<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191064573288">
<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">3 Months Ended</th>
</tr>
<tr><th class="th">
<div>Mar. 31, 2021 </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">67.00%<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">20.00%<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">13.00%<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">87.00%<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>
</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_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>
</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_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>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange3">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_AvailableForSaleSecuritiesDebtMaturitiesAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</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>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentsAllOtherInvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_InvestmentsAllOtherInvestmentsAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
</div></td></tr>
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</div>
</body>
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</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>46
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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">
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191056854856">
<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="1">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</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">$ 1,430,181<span></span>
</td>
<td class="nump">$ 1,533,544<span></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_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">21,965<span></span>
</td>
<td class="nump">24,515<span></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_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(2,110)<span></span>
</td>
<td class="num">(2,821)<span></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_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,450,036<span></span>
</td>
<td class="nump">1,555,238<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_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>
</tr>
<tr class="re">
<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>
</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">1,410,407<span></span>
</td>
<td class="nump">1,513,770<span></span>
</td>
</tr>
<tr class="re">
<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">6,027<span></span>
</td>
<td class="nump">8,577<span></span>
</td>
</tr>
<tr class="ro">
<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">(596)<span></span>
</td>
<td class="num">(140)<span></span>
</td>
</tr>
<tr class="re">
<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">1,415,838<span></span>
</td>
<td class="nump">1,522,207<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_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>
</tr>
<tr class="re">
<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>
</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">888,596<span></span>
</td>
<td class="nump">1,025,454<span></span>
</td>
</tr>
<tr class="re">
<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">2,476<span></span>
</td>
<td class="nump">2,977<span></span>
</td>
</tr>
<tr class="ro">
<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">(107)<span></span>
</td>
<td class="num">(71)<span></span>
</td>
</tr>
<tr class="re">
<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">890,965<span></span>
</td>
<td class="nump">1,028,360<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_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>
</tr>
<tr class="re">
<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>
</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">521,811<span></span>
</td>
<td class="nump">488,316<span></span>
</td>
</tr>
<tr class="re">
<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">3,551<span></span>
</td>
<td class="nump">5,600<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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(489)<span></span>
</td>
<td class="num">(69)<span></span>
</td>
</tr>
<tr class="re">
<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">524,873<span></span>
</td>
<td class="nump">493,847<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] | 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>
</tr>
<tr class="re">
<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>
</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">446,816<span></span>
</td>
<td class="nump">514,182<span></span>
</td>
</tr>
<tr class="re">
<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">1,838<span></span>
</td>
<td class="nump">2,194<span></span>
</td>
</tr>
<tr class="ro">
<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">(76)<span></span>
</td>
<td class="num">(41)<span></span>
</td>
</tr>
<tr class="re">
<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">448,578<span></span>
</td>
<td class="nump">516,335<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] | 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>
</tr>
<tr class="re">
<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>
</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">325,335<span></span>
</td>
<td class="nump">325,079<span></span>
</td>
</tr>
<tr class="re">
<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">3,108<span></span>
</td>
<td class="nump">4,941<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(245)<span></span>
</td>
<td class="num">(40)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">328,198<span></span>
</td>
<td class="nump">329,980<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] | 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>
</tr>
<tr class="re">
<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>
</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">80,703<span></span>
</td>
<td class="nump">94,234<span></span>
</td>
</tr>
<tr class="re">
<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">292<span></span>
</td>
<td class="nump">354<span></span>
</td>
</tr>
<tr class="ro">
<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">(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_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">80,993<span></span>
</td>
<td class="nump">94,586<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] | 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>
</tr>
<tr class="re">
<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>
</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">96,698<span></span>
</td>
<td class="nump">80,099<span></span>
</td>
</tr>
<tr class="re">
<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">36<span></span>
</td>
<td class="nump">185<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(164)<span></span>
</td>
<td class="num">(9)<span></span>
</td>
</tr>
<tr class="re">
<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">96,570<span></span>
</td>
<td class="nump">80,275<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] | 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>
</tr>
<tr class="re">
<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>
</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">234,164<span></span>
</td>
<td class="nump">307,576<span></span>
</td>
</tr>
<tr class="re">
<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">126<span></span>
</td>
<td class="nump">233<span></span>
</td>
</tr>
<tr class="ro">
<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="num">(9)<span></span>
</td>
</tr>
<tr class="re">
<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">234,290<span></span>
</td>
<td class="nump">307,800<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_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>
</tr>
<tr class="re">
<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>
</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">59,030<span></span>
</td>
<td class="nump">50,318<span></span>
</td>
</tr>
<tr class="re">
<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">326<span></span>
</td>
<td class="nump">383<span></span>
</td>
</tr>
<tr class="ro">
<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">(35)<span></span>
</td>
<td class="num">(4)<span></span>
</td>
</tr>
<tr class="re">
<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">59,321<span></span>
</td>
<td class="nump">50,697<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] | 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>
</tr>
<tr class="re">
<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>
</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">121,776<span></span>
</td>
<td class="nump">104,271<span></span>
</td>
</tr>
<tr class="re">
<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">220<span></span>
</td>
<td class="nump">196<span></span>
</td>
</tr>
<tr class="ro">
<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">(22)<span></span>
</td>
<td class="num">(12)<span></span>
</td>
</tr>
<tr class="re">
<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">121,974<span></span>
</td>
<td class="nump">104,455<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] | 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>
</tr>
<tr class="re">
<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>
</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">34,515<span></span>
</td>
<td class="nump">31,779<span></span>
</td>
</tr>
<tr class="re">
<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">81<span></span>
</td>
<td class="nump">91<span></span>
</td>
</tr>
<tr class="ro">
<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">(25)<span></span>
</td>
<td class="num">(16)<span></span>
</td>
</tr>
<tr class="re">
<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">34,571<span></span>
</td>
<td class="nump">31,854<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] | 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>
</tr>
<tr class="re">
<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>
</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">5,137<span></span>
</td>
<td class="nump">5,191<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_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="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_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="num">(7)<span></span>
</td>
</tr>
<tr class="re">
<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">5,130<span></span>
</td>
<td class="nump">5,184<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] | 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>
</tr>
<tr class="re">
<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>
</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">6,233<span></span>
</td>
<td class="nump">1,041<span></span>
</td>
</tr>
<tr class="re">
<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="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_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(20)<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_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6,213<span></span>
</td>
<td class="nump">1,041<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_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>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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">19,774<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">15,938<span></span>
</td>
</tr>
<tr class="ro">
<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">(1,514)<span></span>
</td>
<td class="num">(2,681)<span></span>
</td>
</tr>
<tr class="re">
<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">34,198<span></span>
</td>
<td class="nump">33,031<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=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>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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">(1,514)<span></span>
</td>
<td class="num">(2,681)<span></span>
</td>
</tr>
<tr class="re">
<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">3,198<span></span>
</td>
<td class="nump">2,031<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=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>
</tr>
<tr class="re">
<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>
</tr>
<tr class="ro">
<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">15,062<span></span>
</td>
</tr>
<tr class="re">
<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">15,938<span></span>
</td>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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">$ 31,000<span></span>
</td>
</tr>
<tr><td colspan="3"></td></tr>
<tr><td colspan="3"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">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 condensed 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.</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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr><td><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>
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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 (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>
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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>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>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
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</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>
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<td><strong> Data Type:</strong></td>
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</tr>
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</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
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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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</div></td></tr>
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<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>
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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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<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>
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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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNi</td>
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<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>
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<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>
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<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">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember</td>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191061849288">
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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Investments, Investments Temporarily Impaired (Details)<br> $ in Thousands</strong></div></th>
<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($) </div>
<div>Investment</div>
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</tr>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
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<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableforsaleSecuritiesInUnrealizedLossPositionsQualitativeDisclosureNumberOfPositions1', window );">Number of investments | Investment</a></td>
<td class="nump">101<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionLessThanTwelveMonthsFairValue', window );">Estimated fair value, less than 12 months of temporary impairment</a></td>
<td class="nump">$ 233,665<span></span>
</td>
</tr>
<tr class="re">
<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">$ (321)<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">7<span></span>
</td>
</tr>
<tr class="re">
<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">$ 60,681<span></span>
</td>
</tr>
<tr class="ro">
<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">$ (166)<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">6<span></span>
</td>
</tr>
<tr class="ro">
<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">$ 52,838<span></span>
</td>
</tr>
<tr class="re">
<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">$ (35)<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">297<span></span>
</td>
</tr>
<tr class="re">
<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">$ 76,712<span></span>
</td>
</tr>
<tr class="ro">
<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">$ (47)<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">3<span></span>
</td>
</tr>
<tr class="ro">
<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">$ 11,343<span></span>
</td>
</tr>
<tr class="re">
<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">$ (27)<span></span>
</td>
</tr>
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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> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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<a href="javascript:void(0);" onclick="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>
</tr>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
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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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<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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<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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<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_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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<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><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USTreasurySecuritiesMember</td>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTypeAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
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<tr>
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<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140190980646008">
<tr>
<th class="tl" colspan="2" rowspan="1"><div style="width: 200px;"><strong>Fair Value Measurements (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2"><div>Mar. 31, 2021</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2020</div></th>
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<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 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="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
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<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
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<tr class="re">
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<td class="th" style="border-bottom: 0px;"><sup></sup></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>
</tr>
<tr 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="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_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr 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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member', window );">Significant Other Observable Inputs (Level 2) [Member] | 1 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="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_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 314,600<span></span>
</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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member', window );">Significant Other Observable Inputs (Level 2) [Member] | 0.125 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="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_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">527,300<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr 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 );">Recurring Basis [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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>[1]</sup></td>
<td class="nump">372,050<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 221,125<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 Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">3,198<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,031<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">1,791,086<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,745,363<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 );">Recurring Basis [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<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>[3]</sup></td>
<td class="nump">776,776<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">846,315<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 );">Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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">10,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">10,000<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 );">Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<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>[4]</sup></td>
<td class="nump">177,563<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">174,861<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 );">Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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">293,611<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">358,497<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 );">Recurring Basis [Member] | 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="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">17,500<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 );">Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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>[4]</sup></td>
<td class="nump">156,545<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">136,309<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 );">Recurring Basis [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<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>[4]</sup></td>
<td class="nump">11,343<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,225<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 );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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">372,050<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">221,125<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 Therapeutics N.V.</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3,198<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,031<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">668,859<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">581,653<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 );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<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 );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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 );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<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">293,611<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">358,497<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 );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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 );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<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 );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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 Therapeutics N.V.</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">1,122,227<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,163,710<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 );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<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">776,776<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">846,315<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 );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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">177,563<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">174,861<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 );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<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 );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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">156,545<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">136,309<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 );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="re">
<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">11,343<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,225<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 );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
</tr>
<tr class="ro">
<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="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">$ 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><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 condensed 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 condensed 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 was included in cash and cash equivalents, with the difference included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top">Included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[5]</td>
<td style="vertical-align: top;" valign="top">$17.5 million included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</td>
</tr>
</table></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>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">
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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">
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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>
<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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNi</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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<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of notes payable.</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 210.5-02.19,20,22)<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>
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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><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel1Member</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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<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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel3Member</td>
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<DOCUMENT>
<TYPE>XML
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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">
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191061956344">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements (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="1"></th>
</tr>
<tr>
<th class="th">
<div>Apr. 30, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($) </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Mar. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">$ 111,607<span></span>
</td>
<td class="nump">$ 133,367<span></span>
</td>
<td class="text">&#160;<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>
</tr>
<tr 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">59,986<span></span>
</td>
<td class="nump">66,008<span></span>
</td>
<td class="text">&#160;<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="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">$ 27,159<span></span>
</td>
<td class="nump">49,406<span></span>
</td>
<td class="text">&#160;<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>
</tr>
<tr 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 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="nump">8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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">$ 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 " 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">78,100<span></span>
</td>
<td class="nump">$ 87,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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">$ 447,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 465,800<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_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>
</tr>
<tr 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">70.00%<span></span>
</td>
<td class="nump">66.00%<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] | 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>
</tr>
<tr 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">$ 60,000<span></span>
</td>
<td class="nump">$ 66,000<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_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>
</tr>
<tr 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">$ 18,100<span></span>
</td>
<td class="nump">$ 21,400<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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember', window );">2013 Strategic Neurology [Member] | 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>
</tr>
<tr 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 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="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>
</tr>
<tr 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] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_MilestonePaymentAchieved', window );">Milestone payment achieved</a></td>
<td class="nump">$ 10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_MilestonePaymentAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 payment achieved 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;">ions_MilestonePaymentAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_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_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_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>
</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_CollaborativeArrangementsAndLicensingAgreementsBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsBiogenMember</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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementAndLicensingAgreementEnteredIntoInSeptember2013WithBiogenMember</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_StatementScenarioAxis=us-gaap_ScenarioPlanMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_StatementScenarioAxis=us-gaap_ScenarioPlanMember</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_Ion541Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_Ion541Member</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_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
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<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191057698040">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt (Details) - USD ($)<br> $ / shares in Units, shares in Millions, $ in Millions</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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="text">&#160;<span></span>
</td>
<td class="nump">$ 52.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " 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="text">&#160;<span></span>
</td>
<td class="nump">108.7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " 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="text">&#160;<span></span>
</td>
<td class="nump">$ 56.1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember', window );">Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_CallSpread', window );">Cost of call spread</a></td>
<td class="nump">$ 46.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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">136.7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">89.8<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="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_ConvertibleSeniorNotes0PercentMember', window );">0% Convertible Senior Notes [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">632.5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 );">Outstanding principal balance</a></td>
<td class="nump">$ 632.5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">Apr. 30,  2026<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">0.00%<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)</a></td>
<td class="nump">$ 57.84<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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 );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="nump">$ 76.39<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="nump">10.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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="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>
</tr>
<tr 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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 548.8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Dec. 31,  2024<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="re">
<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)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 83.28<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 123.38<span></span>
</td>
<td class="text">&#160;<span></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_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8.1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 309.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Nov. 30,  2021<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 66.81<span></span>
</td>
<td class="text">&#160;<span></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_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0.8<span></span>
</td>
<td class="text">&#160;<span></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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="nump">$ 247.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible notes</a></td>
<td class="nump">257.0<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_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="nump">$ 62.0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="nump">0.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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>
<td style="white-space:nowrap;">ions_CallSpread</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>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_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>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_DebtInstrumentConvertibleSharesSubjectToConversion">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 of common stock subject to conversion 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>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertibleSharesSubjectToConversion</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentCarryingAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentConvertibleConversionPrice1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentConvertibleConversionPrice1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>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_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_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_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_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_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>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 from the repayment of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="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_RepaymentsOfConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ConvertibleSeniorNotes0PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<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_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>
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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>
</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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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191057365560">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Severance and Retention Costs, Akcea Acquisition (Details) - Akcea Acquisition [Member] - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</tr>
<tr class="ro">
<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 );">Total estimated expenses</a></td>
<td class="nump">$ 28.5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1', window );">Remaining estimated expenses to be recognized through October 2021</a></td>
<td class="nump">7.8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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">14.7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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 );">Amounts expensed during the period</a></td>
<td class="nump">6.1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringReserveAccrualAdjustment1', window );">Reserve adjustments during the period</a></td>
<td class="num">(0.7)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RestructuringReserveNetExpense', window );">Net amount expensed during the period</a></td>
<td class="nump">5.4<span></span>
</td>
<td class="nump">$ 15.3<span></span>
</td>
</tr>
<tr class="ro">
<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">(9.0)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringReserve', window );">Ending balance</a></td>
<td class="nump">11.1<span></span>
</td>
<td class="nump">$ 14.7<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionMember', window );">R&amp;D Expenses [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_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>
</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_RestructuringReserveNetExpense', window );">Net amount expensed during the period</a></td>
<td class="nump">2.5<span></span>
</td>
<td class="text">&#160;<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_AkceaAcquisitionMember', window );">SG&amp;A Expenses [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_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>
</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_RestructuringReserveNetExpense', window );">Net amount expensed during the period</a></td>
<td class="nump">$ 2.9<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_RestructuringReserveNetExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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, net of adjustments to a previously accrued restructuring liability. The net expense increases (decreases) the accrual for restructuring costs.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RestructuringReserveNetExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_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_RestructuringAndRelatedCostExpectedCostRemaining1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 expected cost remaining for the specified restructuring cost.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_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>
</tr>
<tr>
<td style="padding-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_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_RestructuringReserveAccrualAdjustment1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 (reversal of expense) which increases (decreases) the restructuring reserve from an adjustment to a previously accrued restructuring liability.</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)<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)(2))<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_RestructuringReserveAccrualAdjustment1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_RestructuringCostAndReserveAxis=ions_AkceaAcquisitionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_AkceaAcquisitionMember</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_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>
</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_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>
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<span style="display: none;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191061533112">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Severance and Retention Costs, Restructured European Operations (Details) - Restructured European Operations [Member] - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</tr>
<tr class="ro">
<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 );">Total estimated expenses</a></td>
<td class="nump">$ 13.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1', window );">Remaining estimated expenses to be recognized through October 2021</a></td>
<td class="nump">0.4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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">12.4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCharges', window );">Amounts expensed during the period</a></td>
<td class="nump">2.2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringReserveAccrualAdjustment1', window );">Reserve adjustments during the period</a></td>
<td class="num">(1.5)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RestructuringReserveNetExpense', window );">Net amount expensed during the period</a></td>
<td class="nump">0.7<span></span>
</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">(11.9)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">1.2<span></span>
</td>
<td class="nump">$ 12.4<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_RestructuredEuropeanOperationsMember', window );">R&amp;D Expenses [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_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>
</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_RestructuringReserveNetExpense', window );">Net amount expensed during the period</a></td>
<td class="nump">0.1<span></span>
</td>
<td class="text">&#160;<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_RestructuredEuropeanOperationsMember', window );">SG&amp;A Expenses [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_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>
</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_RestructuringReserveNetExpense', window );">Net amount expensed during the period</a></td>
<td class="nump">$ 0.6<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_RestructuringReserveNetExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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, net of adjustments to a previously accrued restructuring liability. The net expense increases (decreases) the accrual for restructuring costs.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RestructuringReserveNetExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_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_RestructuringAndRelatedCostExpectedCostRemaining1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 expected cost remaining for the specified restructuring cost.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_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>
</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>
<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_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_RestructuringReserveAccrualAdjustment1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 (reversal of expense) which increases (decreases) the restructuring reserve from an adjustment to a previously accrued restructuring liability.</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)<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)(2))<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_RestructuringReserveAccrualAdjustment1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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_RestructuringCostAndReserveAxis=ions_RestructuredEuropeanOperationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_RestructuredEuropeanOperationsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
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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>
</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;">us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember</td>
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<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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<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;">v3.21.1</span><table class="report" border="0" cellspacing="2" id="idm140191061440024">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Severance and Retention Costs, Restructured North American TEGSEDI Operations (Details) - Restructured North American TEGSEDI Operations [Member]<br> $ in Millions</strong></div></th>
<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostAndReserveAxis=ions_RestructuredNorthAmericanTEGSEDIOperationsMember', window );">Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringCostsAbstract', window );"><strong>Severance and Retention Costs [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RestructuringAndRelatedCostExpectedCost1', window );">Total estimated expenses</a></td>
<td class="nump">$ 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_RestructuringCostAndReserveAxis=ions_RestructuredNorthAmericanTEGSEDIOperationsMember', 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 [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 );">Total estimated expenses</a></td>
<td class="nump">$ 14<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
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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>
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
