<SEC-DOCUMENT>0000874015-22-000104.txt : 20220504
<SEC-HEADER>0000874015-22-000104.hdr.sgml : 20220504
<ACCEPTANCE-DATETIME>20220504171119
ACCESSION NUMBER:		0000874015-22-000104
CONFORMED SUBMISSION TYPE:	10-Q
PUBLIC DOCUMENT COUNT:		55
CONFORMED PERIOD OF REPORT:	20220331
FILED AS OF DATE:		20220504
DATE AS OF CHANGE:		20220504

FILER:

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

	FILING VALUES:
		FORM TYPE:		10-Q
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		22892553

	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 3-31-2022
<TEXT>
<XBRL>
<html xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldi="http://xbrl.org/2006/xbrldi" xmlns:iso4217="http://www.xbrl.org/2003/iso4217" xmlns:ix="http://www.xbrl.org/2013/inlineXBRL" xmlns:ixt="http://www.xbrl.org/inlineXBRL/transformation/2015-02-26" xmlns:ixt-sec="http://www.sec.gov/inlineXBRL/transformation/2015-08-31" xmlns:us-gaap="http://fasb.org/us-gaap/2021-01-31" xmlns:dei="http://xbrl.sec.gov/dei/2021q4" xmlns:utr="http://www.xbrl.org/2009/utr" xmlns:country="http://xbrl.sec.gov/country/2021" xmlns:currency="http://xbrl.sec.gov/currency/2021" xmlns:naics="http://xbrl.sec.gov/naics/2021" xmlns:sic="http://xbrl.sec.gov/sic/2021" xmlns:stpr="http://xbrl.sec.gov/stpr/2021" xmlns:exch="http://xbrl.sec.gov/exch/2021" xmlns:srt="http://fasb.org/srt/2021-01-31" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:ions="http://ionispharma.com/20220331" xmlns="http://www.w3.org/1999/xhtml">
<head>
    <title></title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using EDGARfilings PROfile 8.2.0.0
         Copyright 1995 - 2022 Broadridge -->
    <meta http-equiv="Content-Type" content="text/html" />
</head>
<body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; background-color: #FFFFFF;">
<div id="DSPFiXBRLHidden" style="display: none;"><ix:header><ix:hidden><ix:nonNumeric name="dei:AmendmentFlag" id="Fact_f0028d42fdf94d64b2e43d0c644f41ff" contextRef="c20220101to20220331" format="ixt:booleanfalse">false</ix:nonNumeric><ix:nonNumeric name="dei:CurrentFiscalYearEndDate" id="Fact_8e41f7c37386421e81c89573ae2e32fa" contextRef="c20220101to20220331" format="ixt:datemonthday">12-31</ix:nonNumeric><ix:nonNumeric name="dei:DocumentFiscalYearFocus" id="Fact_4ae580782bac4f62861c520f102b5a43" contextRef="c20220101to20220331">2022</ix:nonNumeric><ix:nonNumeric name="dei:DocumentFiscalPeriodFocus" id="Fact_307b3d7761e048a9a1981817f8746bff" contextRef="c20220101to20220331">Q1</ix:nonNumeric><ix:nonNumeric name="dei:EntityCentralIndexKey" id="Fact_5b9de3963cb8400e85b7297a1c736a9e" contextRef="c20220101to20220331">0000874015</ix:nonNumeric><ix:nonNumeric name="ions:PeriodAfterBillingWhenPaymentIsReceived" id="Fact_cb46feec840d4d05b86df2a2af3b44c3" contextRef="c20220101to20220331">P3M</ix:nonNumeric><ix:nonFraction name="us-gaap:NumberOfOperatingSegments" id="Fact_ba6a4e8bb35940dbbf919d263b57d70e" contextRef="c20220101to20220331" unitRef="U012" decimals="INF">1</ix:nonFraction><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_3ea144f70898401099a1731ad0c7e39f" contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheThreeMember" unitRef="U003" decimals="3">0.333</ix:nonFraction><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_b2b6dbe875764e78b9cce0b8464216dd" contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" unitRef="U003" decimals="3">0.333</ix:nonFraction><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_b531c97d5a394e3f8a5454ecd82ddb93" contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheTwoMember" unitRef="U003" decimals="3">0.333</ix:nonFraction><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange3" id="Fact_f12cc57cfa544d218ac6c26f9aae5797" contextRef="c20220101to20220331">P3Y6M</ix:nonNumeric><ix:nonNumeric name="us-gaap:DebtInstrumentMaturityDate" id="Fact_109f9369bddf4793b7c1ba8f66869fde" contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember">2026-04-30</ix:nonNumeric><ix:nonNumeric name="us-gaap:DebtInstrumentMaturityDate" id="Fact_c5b254d960d242d380e7e1f35dc8b7ec" contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember">2024-12-31</ix:nonNumeric></ix:hidden><ix:references><link:schemaRef xlink:href="ions-20220331.xsd" xlink:type="simple"></link:schemaRef></ix:references><ix:resources><xbrli:context id="c20220101to20220331"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220428"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2022-04-28</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CollaborativeAgreementRevenueMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CollaborativeAgreementRevenueMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_SpinrazaRoyaltiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SpinrazaRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:EplontersenJointDevelopmentRevenueMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ProductOrServiceAxis_SpinrazaRoyaltiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SpinrazaRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:EplontersenJointDevelopmentRevenueMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_ProductMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ProductOrServiceAxis_ProductMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_CommercialMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ProductOrServiceAxis_CommercialMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20201231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2020-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20201231_StatementEquityComponentsAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2020-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20201231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2020-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_StatementEquityComponentsAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_StatementEquityComponentsAxis_RetainedEarningsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20201231_StatementEquityComponentsAxis_RetainedEarningsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2020-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20201231"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2020-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220331_StatementEquityComponentsAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_StatementEquityComponentsAxis_RetainedEarningsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210331_StatementEquityComponentsAxis_RetainedEarningsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210331"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:instant>2021-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210331_StatementEquityComponentsAxis_CommonStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20211001to20211231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:Ion306Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-10-01</xbrli:startDate><xbrli:endDate>2021-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:AstrazenecaCollaborationEplontersenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:AlnylamCollaborationMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2020-10-01</xbrli:startDate><xbrli:endDate>2020-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_Ion859Member"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:Ion859Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaboration2013StrategicNeurologyMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20181001to20181231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:RocheCollaborationIonisFbLForComplementMediatedDiseasesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-10-01</xbrli:startDate><xbrli:endDate>2018-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20211001to20211231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaboration2018StrategicNeurologyMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-10-01</xbrli:startDate><xbrli:endDate>2021-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20180401to20180630_MajorCustomersAxis_BiogenIncMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:MajorCustomersAxis">ions:BiogenIncMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2018-04-01</xbrli:startDate><xbrli:endDate>2018-06-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:AstrazenecaCollaborationEplontersenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:AstrazenecaCollaborationEplontersenMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:AccountsReceivableMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:MajorCustomersAxis">ions:TwoSignificantCustomersMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CreditConcentrationRiskMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:AccountsReceivableMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CreditConcentrationRiskMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:MajorCustomersAxis">ions:TwoSignificantCustomersMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20211231"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20200101to20201231"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2020-01-01</xbrli:startDate><xbrli:endDate>2020-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20200101to20201231_FinancialInstrumentAxis_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2020-01-01</xbrli:startDate><xbrli:endDate>2020-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20211231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PublicUtilitiesInventoryAxis">ions:CommercialRawMaterialsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PublicUtilitiesInventoryAxis">ions:ClinicalRawMaterialsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PublicUtilitiesInventoryAxis">ions:CommercialRawMaterialsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PublicUtilitiesInventoryAxis">ions:ClinicalRawMaterialsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">us-gaap:BuildingMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">us-gaap:BuildingMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">us-gaap:ShareBasedPaymentArrangementEmployeeMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">us-gaap:ShareBasedPaymentArrangementEmployeeMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_EmployeeStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_AwardTypeAxis_EmployeeStockMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheThreeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:VestingAxis">us-gaap:ShareBasedCompensationAwardTrancheThreeMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheOneMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:VestingAxis">us-gaap:ShareBasedCompensationAwardTrancheOneMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheTwoMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:VestingAxis">us-gaap:ShareBasedCompensationAwardTrancheTwoMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MinimumMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:RangeAxis">srt:MinimumMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">ions:ShareBasedPaymentArrangementBoardOfDirectorMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MaximumMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:RangeAxis">srt:MaximumMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">ions:ShareBasedPaymentArrangementBoardOfDirectorMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">us-gaap:ShareBasedPaymentArrangementEmployeeMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:RangeAxis">srt:MaximumMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:RangeAxis">srt:MinimumMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220331_AwardTypeAxis_EmployeeStockOptionMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_AwardTypeAxis_PerformanceSharesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentExpensesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">us-gaap:SellingGeneralAndAdministrativeExpensesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_IncomeStatementLocationAxis_CostOfSalesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">us-gaap:CostOfSalesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">us-gaap:SellingGeneralAndAdministrativeExpensesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentExpensesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_IncomeStatementLocationAxis_CostOfSalesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">us-gaap:CostOfSalesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_EquitySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:EquitySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPrivateCompaniesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPubliclyTradedCompaniesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPubliclyTradedCompaniesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_EquitySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:EquitySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPrivateCompaniesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPrivateCompaniesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPrivateCompaniesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPubliclyTradedCompaniesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPubliclyTradedCompaniesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:EquitySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:EquitySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210401to20210630_ProductOrServiceAxis_Ion541Member_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaboration2013StrategicNeurologyMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:Ion541Member</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-04-01</xbrli:startDate><xbrli:endDate>2021-06-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ProductOrServiceAxis_SpinrazaRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SpinrazaRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ProductOrServiceAxis_SpinrazaRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SpinrazaRoyaltiesMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210101to20210331_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:RevenueFromContractWithCustomerMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-01-01</xbrli:startDate><xbrli:endDate>2021-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:RevenueFromContractWithCustomerMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20211231_TypeOfArrangementAxis_BiogenCollaborationsMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-12-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20220331_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="srt:RangeAxis">srt:MaximumMember</xbrldi:explicitMember><xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaboration2013StrategicNeurologyMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-04-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2021-04-30</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20211101to20211130_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-11-01</xbrli:startDate><xbrli:endDate>2021-11-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-04-01</xbrli:startDate><xbrli:endDate>2021-04-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:instant>2022-03-31</xbrli:instant></xbrli:period></xbrli:context><xbrli:context id="c20210401to20210430"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2021-04-01</xbrli:startDate><xbrli:endDate>2021-04-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20191201to20191231"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier></xbrli:entity><xbrli:period><xbrli:startDate>2019-12-01</xbrli:startDate><xbrli:endDate>2019-12-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20210401to20210630_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2021-04-01</xbrli:startDate><xbrli:endDate>2021-06-30</xbrli:endDate></xbrli:period></xbrli:context><xbrli:context id="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"><xbrli:entity><xbrli:identifier scheme="http://www.sec.gov/CIK">0000874015</xbrli:identifier><xbrli:segment><xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember></xbrli:segment></xbrli:entity><xbrli:period><xbrli:startDate>2022-01-01</xbrli:startDate><xbrli:endDate>2022-03-31</xbrli:endDate></xbrli:period></xbrli:context><xbrli:unit id="U001"><xbrli:measure>xbrli:shares</xbrli:measure></xbrli:unit><xbrli:unit id="U002"><xbrli:measure>iso4217:USD</xbrli:measure></xbrli:unit><xbrli:unit id="U003"><xbrli:measure>xbrli:pure</xbrli:measure></xbrli:unit><xbrli:unit id="U004"><xbrli:divide><xbrli:unitNumerator><xbrli:measure>iso4217:USD</xbrli:measure></xbrli:unitNumerator><xbrli:unitDenominator><xbrli:measure>xbrli:shares</xbrli:measure></xbrli:unitDenominator></xbrli:divide></xbrli:unit><xbrli:unit id="U005"><xbrli:measure>ions:Target</xbrli:measure></xbrli:unit><xbrli:unit id="U006"><xbrli:measure>ions:Agreement</xbrli:measure></xbrli:unit><xbrli:unit id="U007"><xbrli:measure>ions:Component</xbrli:measure></xbrli:unit><xbrli:unit id="U008"><xbrli:measure>ions:PerformanceObligation</xbrli:measure></xbrli:unit><xbrli:unit id="U009"><xbrli:measure>ions:Partner</xbrli:measure></xbrli:unit><xbrli:unit id="U010"><xbrli:measure>ions:Company</xbrli:measure></xbrli:unit><xbrli:unit id="U011"><xbrli:measure>ions:Investment</xbrli:measure></xbrli:unit><xbrli:unit id="U012"><xbrli:measure>ions:Segment</xbrli:measure></xbrli:unit><xbrli:unit id="U013"><xbrli:measure>ions:Period</xbrli:measure></xbrli:unit><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_17f5c15fd8fe452b890ee866cfaa6b85" toRefs="Foot_2ec4116852e041e3a2a38cb16ff4ea22" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_7842515e18104a5cafcff84ddb01d951" toRefs="Foot_2ec4116852e041e3a2a38cb16ff4ea22" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_d8fc413c165c4a2c8aa4472257c08e29" toRefs="Foot_2ec4116852e041e3a2a38cb16ff4ea22" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_b358568c049541b1856e64106205b629" toRefs="Foot_2ec4116852e041e3a2a38cb16ff4ea22" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_5a3e302889e04832960498aaf3fc8b2b" toRefs="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_6d98cfd31fed4be1bc5dd4e5765ff970" toRefs="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_3884240483e242908ec151549d8a9266" toRefs="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_4ce9866198094ab9bb0fba527e9f7a46" toRefs="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_92f2c745baa2467ebc8da9f308582732" toRefs="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_a02ee28d048e4f4a86d13e676be48142" toRefs="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_1b769ef466ea447fba9ad51918866940" toRefs="Foot_f8be77aa66f84482abc56f1b540c3aca" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_144b8361be90457089523a487891e260" toRefs="Foot_f0cb78a83b31476988ccfd169edddb78" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_8ac6126992144e2d902abafe0f05aaf1" toRefs="Foot_5b9b3c8599d14902835320847fbc6b63" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_c11eb07ea3324e24902d31be146e2aba" toRefs="Foot_2009e9e101cd4940acd892bb1ca9a15f" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_3abef904d1ac4dac9365cd6a89ce306b" toRefs="Foot_a07f61350d6c43dcbc95f9a5735b974a" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_ab8b93d31763462f825afbb8d94ca1c5" toRefs="Foot_a07f61350d6c43dcbc95f9a5735b974a" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_063ea3aa6c0446b1901c679162b7098d" toRefs="Foot_4aceaee590d24617870bb41115adebfe" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_18bb66a7c7c8455bbd8d594108704256" toRefs="Foot_4aceaee590d24617870bb41115adebfe" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_5715fb92aca2469f8d6b89bcc32dd2ad" toRefs="Foot_4aceaee590d24617870bb41115adebfe" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_b0bdc20ef3184f16a0c2f40e12be4cfc" toRefs="Foot_4aceaee590d24617870bb41115adebfe" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_642c9681829a411280b706605512aec4" toRefs="Foot_55aad856d839435daad2d772a2ea1bc5" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_2faff3973c0f4ab0bd4fcffd3307bce8" toRefs="Foot_55aad856d839435daad2d772a2ea1bc5" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_b8a712e5f4af42cdb9018ff5937f5e79" toRefs="Foot_20cf8a92586d4d88bc45b040cb662025" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_795298199a7149089987fd608d910788" toRefs="Foot_20cf8a92586d4d88bc45b040cb662025" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_e3f0b01c2b014194af0169f71cb6cace" toRefs="Foot_74bbbb57209c4f53960b9d7c3438ee6b" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship><ix:relationship order="1.0" arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote" fromRefs="Fact_c25f6066e793481b89742397fce1babb" toRefs="Foot_74bbbb57209c4f53960b9d7c3438ee6b" linkRole="http://www.xbrl.org/2003/role/link"></ix:relationship></ix:resources></ix:header></div>
<div class="DSPFPageHeader">
<div><br /></div>
</div>
<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;" />
<div>UNITED STATES</div>
</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>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;">Form <ix:nonNumeric name="dei:DocumentType" id="Fact_28d55d59b48a47e298c5f1f8acda983a" contextRef="c20220101to20220331">10-Q</ix:nonNumeric></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Mark One)</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">
  <tr>
    <td style="width: 20.25pt;"></td>
    <td style="width: 27pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:DocumentQuarterlyReport" id="Fact_5bbd70fef0434e0bb3005d7ef54a8498" contextRef="c20220101to20220331" format="ixt-sec:boolballotbox">&#x2612;</ix:nonNumeric></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">For the Quarterly Period Ended <ix:nonNumeric name="dei:DocumentPeriodEndDate" id="Fact_6e9df661fd6a49358b0d67aa84c8eb02" contextRef="c20220101to20220331" format="ixt:datemonthdayyearen">March 31, 2022</ix:nonNumeric></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">OR</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">
  <tr>
    <td style="width: 20.25pt;"></td>
    <td style="width: 27pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:DocumentTransitionReport" id="Fact_22e4da1d333a4f3ca9ed4cd00d7bb801" contextRef="c20220101to20220331" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF SECURITIES EXCHANGE ACT OF 1934</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">For the transition period from _____ to _____</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Commission file number <ix:nonNumeric name="dei:EntityFileNumber" id="Fact_69eb5d1f30814d11a7d3f1427421815b" contextRef="c20220101to20220331">000-19125</ix:nonNumeric></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;">
  <tr>
    <td style="width: 32.84%; vertical-align: top;">&#160;</td>
    <td style="width: 34.31%; vertical-align: top; border-bottom: #000000 2px solid;">&#160;</td>
    <td style="width: 32.84%; vertical-align: top;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityRegistrantName" id="Fact_423ffc6a28b44260828511a52e661ffa" contextRef="c20220101to20220331">Ionis Pharmaceuticals, Inc.</ix:nonNumeric></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Exact name of Registrant as specified in its charter)</div>
<div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 48.93%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityIncorporationStateCountryCode" id="Fact_5e56b955d0c64e368cbede0122260b2c" contextRef="c20220101to20220331" format="ixt-sec:stateprovnameen">Delaware</ix:nonNumeric></div></td>
    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>
    <td style="width: 48.93%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityTaxIdentificationNumber" id="Fact_2112da11bf8747ad9520c7538638757b" contextRef="c20220101to20220331">33-0336973</ix:nonNumeric></div></td>
  </tr>
  <tr>
    <td style="width: 48.93%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(State or other jurisdiction of incorporation or organization)</div></td>
    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>
    <td style="width: 48.93%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(IRS Employer Identification No.)</div></td>
  </tr>
</table>
<div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> </span><br /></div>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 49%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityAddressAddressLine1" id="Fact_3a6566c78c6c48838724649b631cc6ac" contextRef="c20220101to20220331">2855 Gazelle Court</ix:nonNumeric>, <ix:nonNumeric name="dei:EntityAddressCityOrTown" id="Fact_d65c210a405e49f0ba72838f7eac119f" contextRef="c20220101to20220331">Carlsbad</ix:nonNumeric>, <ix:nonNumeric name="dei:EntityAddressStateOrProvince" id="Fact_8cd659ea51164b91987071f35e2fb911" contextRef="c20220101to20220331" format="ixt-sec:stateprovnameen">California</ix:nonNumeric></div></td>
    <td style="width: 2%; vertical-align: bottom;">&#160;</td>
    <td style="width: 49%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityAddressPostalZipCode" id="Fact_49278299ec2d46a5a610ccdb264e1ac9" contextRef="c20220101to20220331">92010</ix:nonNumeric></div></td>
  </tr>
  <tr>
    <td style="width: 49%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Address of Principal Executive Offices)</div></td>
    <td style="width: 2%; vertical-align: bottom;">&#160;</td>
    <td style="width: 49%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Zip Code)</div></td>
  </tr>
</table>
<div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:CityAreaCode" id="Fact_125734dd54044eaa89da14f2fc3d3bd0" contextRef="c20220101to20220331">760</ix:nonNumeric>-<ix:nonNumeric name="dei:LocalPhoneNumber" id="Fact_a35d14a198d2401d8934c4ba029a537f" contextRef="c20220101to20220331">931-9200</ix:nonNumeric></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Registrant&#8217;s telephone number, including area code)</div>
<div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Securities registered pursuant to Section 12(b) of the Act:</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;">
  <tr>
    <td style="width: 37.58%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Title of each class</div></td>
    <td style="width: 2.08%; vertical-align: bottom;">&#160;</td>
    <td style="width: 19.43%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Trading symbol</div></td>
    <td style="width: 1.94%; vertical-align: bottom;">&#160;</td>
    <td style="width: 38.96%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Name of each exchange on which registered</div></td>
  </tr>
  <tr>
    <td style="width: 37.58%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:Security12bTitle" id="Fact_52255b33c81f4d7cb25d3ed4925c361f" contextRef="c20220101to20220331">Common Stock, $.001 Par Value</ix:nonNumeric></div></td>
    <td style="width: 2.08%; vertical-align: bottom;">&#160;</td>
    <td style="width: 19.43%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8220;<ix:nonNumeric name="dei:TradingSymbol" id="Fact_e3a4cc74d20e45d8bff9336150b85ad0" contextRef="c20220101to20220331">IONS</ix:nonNumeric>&#8221;</div></td>
    <td style="width: 1.94%; vertical-align: bottom;">&#160;</td>
    <td style="width: 38.96%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:SecurityExchangeName" id="Fact_8e4ded3e323748dc86453783a0f00869" contextRef="c20220101to20220331" format="ixt-sec:exchnameen">The Nasdaq Stock Market LLC</ix:nonNumeric></div></td>
  </tr>
</table>
<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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 32.84%; vertical-align: top;">&#160;</td>
    <td style="width: 34.31%; vertical-align: top; border-bottom: #000000 2px solid;">&#160;</td>
    <td style="width: 32.84%; vertical-align: top;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. <ix:nonNumeric name="dei:EntityCurrentReportingStatus" id="Fact_d3ee9e2530ea46e2b590e9f9cb002616" contextRef="c20220101to20220331">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>
<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_191a54ad0b1c4c67aafb02582393d3d5" contextRef="c20220101to20220331">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>
<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 is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of &#8220;large accelerated filer,&#8221; &#8220;accelerated filer,&#8221; &#8220;smaller reporting company,&#8221; and &#8220;emerging growth company&#8221; in Rule 12b-2 of the Exchange Act.</div>
<div><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;">
  <tr>
    <td style="width: 50%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:EntityFilerCategory" id="Fact_25013b9234014ef296d27826b7cec20c" contextRef="c20220101to20220331">Large Accelerated Filer</ix:nonNumeric>&#xA0;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#x2612;</span></div></td>
    <td style="width: 50%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accelerated Filer <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#x2610;</span></div></td>
  </tr>
  <tr>
    <td style="width: 50%; vertical-align: top;">&#160;</td>
    <td style="width: 50%; vertical-align: top;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 50%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-accelerated Filer <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#x2610;</span></div></td>
    <td style="width: 50%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Smaller Reporting Company <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonNumeric name="dei:EntitySmallBusiness" id="Fact_0f4d8a3583d64629b92e13dee079ecb1" contextRef="c20220101to20220331" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></span></div></td>
  </tr>
  <tr>
    <td style="width: 50%; vertical-align: top;">&#160;</td>
    <td style="width: 50%; vertical-align: top;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Emerging Growth Company <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonNumeric name="dei:EntityEmergingGrowthCompany" id="Fact_b324ad6856c946fcb60ff103712caa84" contextRef="c20220101to20220331" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></span></div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#x2610;</span></div>
<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 is a shell company (as defined in Rule 12(b)-2 of the Securities Exchange Act of 1934). Yes <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonNumeric name="dei:EntityShellCompany" id="Fact_3bc115f63d5d44be8cdbc2eba0d2aab7" contextRef="c20220101to20220331" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></span> No <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#x2612;</span></div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The number of shares of voting common stock outstanding as of April 28, 2022 was <ix:nonFraction name="dei:EntityCommonStockSharesOutstanding" id="Fact_3a99a0f5d2b046e59520e673d7e403f7" contextRef="c20220428" unitRef="U001" decimals="INF" scale="0" format="ixt:numdotdecimal">141,797,854</ix:nonFraction>.</div>
<div><br /></div>
<div class="DSPFPageFooter">
<div><br /></div>
</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
</div>
<div class="DSPFPageHeader">
<div><br /></div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Index"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FORM 10-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;">
  <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>
    <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;">&#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;"><a href="#BalanceSheet" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Balance Sheets</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> as of </span>March 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited) and </span>December 31, 2021</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>
  <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;"><a href="#IncomeStatementQ1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Operations</a><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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></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;"><a href="#ComprehensiveIncomeQ1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Comprehensive Loss</a><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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></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;"><a href="#EquityQ1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Stockholders&#8217; Equity</a><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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></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;"><a href="#CashFlows" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of Cash Flows</a><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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></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;"><a href="#Notes" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Notes to Condensed Consolidated Financial Statements (unaudited)</a></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>
  <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 2:</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;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations:</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;">&#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;"><a href="#Overview" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Overview</a></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;">25</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;"><a href="#ResultsofOperations" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Results of Operations</a></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;">29</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;"><a href="#Liquidity" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liquidity and Capital Resources</a></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;">34</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;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 3:</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;"><a href="#Item3MarketRisk" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Quantitative and Qualitative Disclosures about Market Risk</a></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>
  </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 4:</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;"><a href="#Item4Controls" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Controls and Procedures</a></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>
  </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; font-weight: bold;">PART II</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;"><a href="#PARTII" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">OTHER INFORMATION</a></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>
  </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;"><a href="#ITEM1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Legal Proceedings</a></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>
  </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 1A:</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;"><a href="#ITEM1A" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk Factors</a></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;">37</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;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 2:</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;"><a href="#ITEM2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unregistered Sales of Equity Securities and Use of Proceeds</a></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;">55</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;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 3:</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;"><a href="#ITEM3" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Default upon Senior Securities</a></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;">55</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;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 4:</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;"><a href="#ITEM4" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mine Safety Disclosures</a></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;">55</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;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 5:</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;"><a href="#ITEM5" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other Information</a></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;">55</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;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 6:</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;"><a href="#ITEM6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exhibits</a></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;">56</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 colspan="2" style="width: 92.08%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#SIGNATURES" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">SIGNATURES</a></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;">57</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">TRADEMARKS</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#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><br /></div>
<div class="DSPFPageFooter">
<div><br /></div>
</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
</div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="BalanceSheet"><!--Anchor--></a><!--PROfilePageNumberReset%Num%3%%%-->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><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31,</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</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; text-indent: 4.5pt;"><span style="text-indent: 0pt;">December 31</span>,</div><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>
  </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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(unaudited)</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="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: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASSETS</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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current assets:</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash and cash equivalents</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:CashAndCashEquivalentsAtCarryingValue" id="Fact_58ab72fa50f24ffe98199f48fbe2c7f0" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">542,513</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:CashAndCashEquivalentsAtCarryingValue" id="Fact_a0cb8c640e1a44688ea7c7919293748f" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">869,191</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_05d3c63942424d44b3a45d0e399d7509" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,509,880</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:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_40b92a7d67634da98603b4b62a18fd2a" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,245,782</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: 18pt; 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:ContractWithCustomerAssetNetCurrent" id="Fact_42eb7b27d7ea459086945663ae763056" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,122</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:ContractWithCustomerAssetNetCurrent" id="Fact_90c87b1639e7454d862938e1695fb4ba" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">61,896</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Inventories</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:InventoryNet" id="Fact_bdc1851ec3a24426938e66ad4005713a" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,032</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:InventoryNet" id="Fact_efd195f3edec4c3091ff79a53462abb8" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,806</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%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current assets</div></td>
    <td 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:OtherAssetsCurrent" id="Fact_c0fa7bfa145e4eada7d79dd483724b5a" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">150,577</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;">&#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:OtherAssetsCurrent" id="Fact_a989f48740884b3f9c662b56d8ec6f22" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">143,374</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%;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current assets</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:AssetsCurrent" id="Fact_4a277ae70920496a859de16b126a781a" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,253,124</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:AssetsCurrent" id="Fact_e034b0a9b6284d72a53c220d22bd9ae4" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,345,049</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;">Property, plant and equipment, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_4cf8028d82514177b93946aa1df7c264" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">177,724</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:PropertyPlantAndEquipmentNet" id="Fact_5ad23e93b4e4467b9feec47f0d291fee" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">178,069</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;">Patents, 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:FiniteLivedIntangibleAssetsNet" id="Fact_edce7eb26c0445978fe4ae3f9eed3d07" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">29,295</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:FiniteLivedIntangibleAssetsNet" id="Fact_7f0d3ff8c03f42ccb4e063d20c964f58" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">29,005</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%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deposits and other assets</div></td>
    <td 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:OtherAssetsNoncurrent" id="Fact_d40d8e0c343c4faa8c8a1998eaa5093e" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">58,949</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:OtherAssetsNoncurrent" id="Fact_20e82d483df24cd682d948f6abcde7a0" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">59,567</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 assets</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:Assets" id="Fact_e57f61237ed14bad8578d2b47564ba8a" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,519,092</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:Assets" id="Fact_bacec939ac84418cbf35df017212761d" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,611,690</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
  <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>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">LIABILITIES AND STOCKHOLDERS&#8217; EQUITY</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current liabilities:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <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;">Accounts 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%;"><div style="font-family: '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:AccountsPayableCurrent" id="Fact_e36e66d0552f404099023f535d194dfe" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16,125</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccountsPayableCurrent" id="Fact_0c0b6424e746450abd937b9f839aed88" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,904</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: 18pt; 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%; 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="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16,525</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:EmployeeRelatedLiabilitiesCurrent" id="Fact_e06d0b21026d4d1db2ff5f69431f6629" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">38,810</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued liabilities</div></td>
    <td colspan="1" valign="bottom" 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:AccruedLiabilitiesCurrent" id="Fact_2fefcdea93734fcd9274bd7403d639f5" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">99,256</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:AccruedLiabilitiesCurrent" id="Fact_213f5a6701c24aa0979bad8e60ab97c3" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">88,560</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes 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;">&#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:AccruedIncomeTaxesCurrent" id="Fact_2af0ce9cd98b44bd81fc94205bb5c219" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">901</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:AccruedIncomeTaxesCurrent" id="Fact_7acc385f5ade40c4a52676f52d77facb" contextRef="c20211231" 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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current portion of long-term obligations</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:LongTermObligationsExcludingConvertibleDebtCurrent" id="Fact_bfee8ed3f29a415ba60a766b5e0cc4b7" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,206</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="ions:LongTermObligationsExcludingConvertibleDebtCurrent" id="Fact_41e0bc055640457ebe9012a9d8313b03" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,526</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%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current portion of deferred contract revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <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:ContractWithCustomerLiabilityCurrent" id="Fact_09d676ed2f6648e5b73076a656df1277" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">91,437</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:ContractWithCustomerLiabilityCurrent" id="Fact_0b483c68b6994735bd21436d4b811df6" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">97,714</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%;"><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%;">&#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:LiabilitiesCurrent" id="Fact_b563c92d4e8b4add87b63f57c52a0e82" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">228,450</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:LiabilitiesCurrent" id="Fact_d521a592d7c446a7b398adb17b375e32" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">240,550</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 deferred contract revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityNoncurrent" id="Fact_8aa6408241e44715ba99551864adcae8" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">333,138</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:ContractWithCustomerLiabilityNoncurrent" id="Fact_ede8dfed22c34e9582c277c64ee5a671" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">351,879</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;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_17a2fd610eef4cd7a40de4f517482a78" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_25be9d36b918409db46b807933199820" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction></ix:nonFraction> percent</span> 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_a398a9b03d9944b0a160b5b317b0ca9e" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">619,898</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_6c57d7bc997a408eac5f0d23f91ceea6" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">619,119</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;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_65f01bf923dd44568923a6ad8fa6fbdd" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4a872f1b79fe480980648870d88ebb8f" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction></ix:nonFraction> percent</span> convertible senior notes, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebtNoncurrent" id="Fact_714a80b1e06f495582600aaf17011943" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">542,860</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="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">542,314</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term obligations, less current portion</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsExcludingConvertibleDebtNoncurrent" id="Fact_fd5cf7d013b54a0388cfec028fd6a1c3" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">25,710</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="ions:LongTermObligationsExcludingConvertibleDebtNoncurrent" id="Fact_54d2771a1e14483ab99a8f4e34dd5224" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,378</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%; 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;">Long-term mortgage 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>
    <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:LongTermLoansFromBank" id="Fact_5af98209ca0a49319c15718880999db5" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">59,462</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:LongTermLoansFromBank" id="Fact_b3ea6b13b4de4225adb6586558c16a06" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">59,713</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%;"><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%;">&#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:Liabilities" id="Fact_b675286a500340028e4203fe4698ca8a" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,809,518</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:Liabilities" id="Fact_f7cd0990ec2c4e71bcb30f7b03262cba" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,839,953</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;">Stockholders&#8217; equity:</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common stock, $<span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockParOrStatedValuePerShare" id="Fact_89ceac2a6de84664a3444e0197c5952f" contextRef="c20211231" unitRef="U004" decimals="3" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockParOrStatedValuePerShare" id="Fact_81d34c4177db42eb9566a4ebacfe9a61" contextRef="c20220331" unitRef="U004" decimals="3" scale="0" format="ixt:numdotdecimal">0.001</ix:nonFraction></ix:nonFraction></span> par value; <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_c1d115fce5ca4643b306e1dda169e403" contextRef="c20211231" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_967e3bfa845149deb2a16ff5f6733824" contextRef="c20220331" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal">300,000,000</ix:nonFraction></ix:nonFraction></span> shares authorized, <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_7433a63c4a1045d2ab18a5f4dd2cfef3" contextRef="c20220331" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_aeabe9bc47984305a06e132d4d7bbbd3" contextRef="c20220331" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal">141,753,122</ix:nonFraction></ix:nonFraction></span> and <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_16b1e67a7f564bfb8ebe67a950cecb91" contextRef="c20211231" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_987e70eb15fa4d6f8f4dee73a63054d5" contextRef="c20211231" unitRef="U001" decimals="0" scale="0" format="ixt:numdotdecimal">141,210,015</ix:nonFraction></ix:nonFraction></span> shares issued and outstanding at <span style="text-indent: 0pt;">March 31, 2022</span> (unaudited) and <span style="text-indent: 0pt;">December 31, 2021</span>, respectively</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:CommonStockValue" id="Fact_2ef68db29f344e1f9b9804fb82fc10d1" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">142</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:CommonStockValue" id="Fact_b57e377e7b024f69a86bf33102ea3c25" contextRef="c20211231" 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%; 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;">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;">&#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:AdditionalPaidInCapitalCommonStock" id="Fact_aebda853ea1647d1b274290dee09ac0f" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,983,078</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:AdditionalPaidInCapitalCommonStock" id="Fact_aee9cda9e03b48d4a74d89f28e31f6ec" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,964,167</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated other comprehensive 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%;">&#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:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_5df551453918447e8a86ae46f488bc1a" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">48,578</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:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_ce487df6de7f42f7b8c77a08d145dc67" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,668</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: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</div></td>
    <td 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:RetainedEarningsAccumulatedDeficit" id="Fact_e5c1467d48e84e9db875c9a95c317d68" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,225,068</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:RetainedEarningsAccumulatedDeficit" id="Fact_49f9d5e423964e58bf47306bfe215fd4" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,159,903</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: 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;">&#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:StockholdersEquity" id="Fact_88e09c1d71dc4fa5bb36f4591af70f7e" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">709,574</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:StockholdersEquity" id="Fact_54e7a9222a6849019c33f1fa21e47093" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">771,737</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; 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 and stockholders&#8217; equity</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesAndStockholdersEquity" id="Fact_1ff304ed0ed84581b2d4f5f331ecaa3f" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,519,092</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LiabilitiesAndStockholdersEquity" id="Fact_8ae3d57392c94bea981bfe93b9c946c0" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,611,690</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">3</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="IncomeStatementQ1"><!--Anchor--></a>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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">&#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: 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_8ccc59285b1c4fde8c989da3abc6e321" contextRef="c20220101to20220331_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">53,818</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e6ae93e981cd404c8ec41482c0c61a6a" contextRef="c20210101to20210331_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">59,986</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: -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;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_98f79b6da3a145ff8d1c7c7ea1a4ae6b" contextRef="c20220101to20220331_ProductOrServiceAxis_ProductMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,160</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_bd9d372310794274aada2c5b2070effc" contextRef="c20210101to20210331_ProductOrServiceAxis_ProductMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">19,838</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%; 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;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c20de44aa08a4feeb6ec553470e9e55b" contextRef="c20220101to20220331_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,307</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_657d26ddec9a4b84ace6ae70602dd9e1" contextRef="c20210101to20210331_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,624</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%;"><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;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_bd6472880fbb416b95f903f2621fca89" contextRef="c20220101to20220331_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">72,285</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_94547c1c92ad438eb4bebba69138f6b7" contextRef="c20210101to20210331_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">84,448</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development 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;">Collaborative agreement revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_a53a80c1d9e842e39354852481bc2e75" contextRef="c20220101to20220331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">49,784</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_bd7b5043e76a49b880159384c891417a" contextRef="c20210101to20210331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">27,159</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%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen joint development 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;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_26c235dd5e1c47a28eeb0d1c47f0907a" contextRef="c20220101to20220331_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">19,850</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_a7adc01605f041fab7dcc375fff7caa0" contextRef="c20210101to20210331_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_1f6c4e6ab7fd4eeba40d80f1b7c50537" contextRef="c20220101to20220331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">69,634</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6baf09d075fa41ccb649de423a487613" contextRef="c20210101to20210331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">27,159</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total 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;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_727ae23d59414052af7ab3decdd56184" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">141,919</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_775c9b23f6344e2c8e38fc7161d48f97" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">111,607</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%;">&#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;">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;">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales</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:CostOfGoodsAndServicesSold" id="Fact_4149679d19a344ec8f07f14a2a4514d5" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,170</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:CostOfGoodsAndServicesSold" id="Fact_68ba2fda58a44024be5ff63f94e807d0" 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%; 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;">Research, development and patent</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:ResearchDevelopmentAndPatentExpense" id="Fact_8fb85da59dd6434798e0931699f46727" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">161,126</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="ions:ResearchDevelopmentAndPatentExpense" id="Fact_40cc4ce1957a47229dc8b59930865f9c" 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%; 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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</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:SellingGeneralAndAdministrativeExpense" id="Fact_061c029e7dfc4b68ae21550ce885f82a" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,127</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:SellingGeneralAndAdministrativeExpense" id="Fact_7f9fe47be1834daca6afdaa55e9445df" 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; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</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:CostsAndExpenses" id="Fact_7b9556ce8cc04ce5a47c736d803a80fb" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">199,423</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:CostsAndExpenses" id="Fact_5ed3ac5e72714296ad9a3ea0d76f60ae" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">203,578</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%;">&#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: 27pt; 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;">&#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:OperatingIncomeLoss" id="Fact_69031d54548341aabeedf33c8c504cfb" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">57,504</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:OperatingIncomeLoss" id="Fact_1c675860760d4b9bb6ea96cd58ebdacd" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">91,971</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#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;">Other income (expense):</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment income</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:InvestmentIncomeNet" id="Fact_d67b485a811f4525906db85d0f12eab9" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,993</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:InvestmentIncomeNet" id="Fact_c1b2d404bb1d44ff8372ae1e91a3906f" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,643</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestExpense" id="Fact_eace0ecd79fe4347aa41212bb38c8b40" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,122</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:InterestExpense" id="Fact_d2c45fb98baf4074b13f019638a4fbfb" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,414</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss on 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:GainLossOnInvestments" id="Fact_4f3cbaabe9b54db0adba894330e3dc9d" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">6,625</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:GainLossOnInvestments" id="Fact_ed4f422854074183a8650e6e88000e26" 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%; 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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other income</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:OtherNonoperatingIncomeExpense" id="Fact_32f8298f1e794b79a00ea0dab0865073" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">187</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:OtherNonoperatingIncomeExpense" id="Fact_baa0473b662842c0b6146ca6484985e5" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3</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%;">&#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;">Loss before income tax expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_eeb95e59b8334ad9a111ffc207cc4439" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">64,071</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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_68a278a750c440a4b9480f5765ab69d5" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">89,739</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#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%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income tax expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_e40b8d3a34a84144a801e3ecfb09d5f7" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,094</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_ced8ef86608a400ea8e16f61515f5e49" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">130</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%;">&#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%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; 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%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_7b9b6b43b3bc4f8db5f0a55a8f20450a" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">65,165</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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_54f0a42c4cb7431e8cdc831d788b765d" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">89,869</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>
  </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%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic and diluted net loss per share</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_dc072bd907c2412c85e96428b2cb98f0" contextRef="c20220101to20220331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_58fe2c982bbe4a918701a6734d89a85f" contextRef="c20220101to20220331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.46</ix:nonFraction></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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_8d42c036be6f4f13acc78e5a8a1ea0d8" contextRef="c20210101to20210331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_88a2d2e2959347e3a70a3eb905fd197a" contextRef="c20210101to20210331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.64</ix:nonFraction></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>
  </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;">Shares used in computing basic and diluted net loss per share</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="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_cd570838ddb649738d00df7a09fcdbb7" contextRef="c20220101to20220331" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_4b2adeca36494082be5f8df1161c9e73" contextRef="c20220101to20220331" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">141,599</ix:nonFraction></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;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_a4cb8cf568b8421b9aef20c6f872b4fc" contextRef="c20210101to20210331" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_d79beadf7224439dae1c75b3c3939771" contextRef="c20210101to20210331" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,770</ix:nonFraction></ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">4</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="ComprehensiveIncomeQ1"><!--Anchor--></a>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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">&#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;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:NetIncomeLoss" id="Fact_915ab404992b41439ff8983bc3d53452" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">65,165</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:NetIncomeLoss" id="Fact_e2219f4b91ac4074bf0182268caca6fc" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">89,869</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized losses on debt securities, net of tax</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" id="Fact_b5442f2d54144714936b29f9dc8919c3" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">15,756</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:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" id="Fact_9fdb4ea0ec7d4dc5b1e180547879efb8" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">3,006</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: 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>
    <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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_8c488c3b36034e08aa370c9ffb2c6875" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">154</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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_3d7f7690411649a3a532188469a6cbe2" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">126</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%;">&#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%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_49ad4947efda47a8b9b2ba8b913e17fd" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">81,075</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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_2b15cd4eb3be402a951f50cf88199c7f" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">93,001</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>
  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">5</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="EquityQ1"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">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, 2021 and 2022</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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Common Stock</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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Additional</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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated Other</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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated</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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Stockholders</span>&#8217;</div></td>
    <td 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; border-bottom: #000000 solid 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description</div></td>
    <td 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;">Shares</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;">Amount</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;">Paid in Capital</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;">Comprehensive Loss</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;">Deficit</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;">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>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at <span style="text-indent: 0pt;">December 31, 2020</span></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:SharesIssued" id="Fact_98dc7656285f417fb1c4f49b8065b1d8" contextRef="c20201231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,366</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:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_c0615757be1444029ca73ff9806fdd30" contextRef="c20201231_StatementEquityComponentsAxis_CommonStockMember" 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%; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_fa026da6ce684909b5fcdddba18fbc9b" contextRef="c20201231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,895,519</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_08332899ffb34f30a41a0135cd7a004c" contextRef="c20201231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">21,071</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_e1c52f1a7e044d809c116cc3f4868079" contextRef="c20201231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,131,306</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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_ce774b980d1945b28dbd6dbee1aff00b" 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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
    <td colspan="1" valign="bottom" 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>
    <td colspan="1" valign="bottom" 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:NetIncomeLoss" id="Fact_4ec345cbb3d84783ab99b6fcd9d52e13" contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember" 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:NetIncomeLoss" id="Fact_ff8ba7d6607349d7a7d35878e7a4fd56" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" 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:NetIncomeLoss" id="Fact_f8b59090577b46a5a21175e258ec3def" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" 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:NetIncomeLoss" id="Fact_a0b1fb196c4248019f70cc81ce4ffdd3" contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">89,869</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:NetIncomeLoss" id="Fact_b1aada9a3f114d9b9e11d3c420555552" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">89,869</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: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized losses, net of tax</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_bc7eeed51da0436cbe39d0f4930cbfad" contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember" 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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_8485bb39a4624b6aa217322973dcb1c8" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" 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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_82090969b9fa4e518410ddb5dd7da186" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">3,006</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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_6c13962c29444067a83835ea2d6a775f" contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_b99f2c3965304e6bb4d58a265f3c82d8" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">3,006</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#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>
    <td colspan="1" valign="bottom" 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_6d20bc87313146299844f8544aba62de" contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember" 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_2ef04cec7e534c4fb3679d4ee1242567" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_50b7616b414448569c7aa087a3d1acb8" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">126</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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_dbd37d1d557f42e89b78ff357c9b5dac" contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_7c24435c391a46c98b5bd04d73d864f3" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">126</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: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_e267472edd1048f38821b09ca0341876" contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">809</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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_09705319fad544f88f52a93356ba29e5" contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_ef64f8607f344130b80bf600834f5f4e" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,758</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_1c877cfc4bf74910b90d494f770b2a0e" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" 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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_c6498dd7baa44d219c112e112d9510a9" contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_7960fc72133543c5a88516ffd647eb32" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,759</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: 28%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div></td>
    <td colspan="1" valign="bottom" 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>
    <td colspan="1" valign="bottom" 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_54f09c577571488cb954476a599f2d5f" contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember" 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_5358d98bd2504580bff7d169c068670d" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" 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>
    <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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_91408da813b4475b88f02413dac41c10" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_d80dd81bdc894762b05120404ed5933a" contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_abe5472affc54cdc9a4597cd351df2b5" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div></td>
    <td 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:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_77b5650ab39c40beb7a58c73a9893326" contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">251</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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_5f0fb82584424913812c7cbe37400a2e" contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember" 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_6d19d713a97144a6a44bb652f9fda88d" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,337</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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_f6dca46437f44b63817ebf5894395adf" contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_08a9b918ec4140e1a9e6142ecc878baf" contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_205aa44f59224abfa0b5dd7f8960b443" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,337</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: 28%; padding-bottom: 4px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at <span style="text-indent: 0pt;">March 31, 2021</span></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="us-gaap:SharesIssued" id="Fact_46fcdfab3930406fadd6b10270850a20" contextRef="c20210331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">140,924</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_95ec257c7d824e90b99af68bc1f7fc7c" contextRef="c20210331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">141</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_a95e0011f0b540229391e10f2c4c7add" 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; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_37499af29a7b4a6e9f1602a1e385dc70" contextRef="c20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">24,203</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_372b0e590ecb4a67982448d69ad3bba4" contextRef="c20210331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,221,175</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_9da1d58b3e7f44069fd02dc6958b717e" 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: 4px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%;"><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 <span style="text-indent: 0pt;">December 31, 2021</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%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_8877c62e6b554930a9b4e66c4ff5d83c" contextRef="c20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">141,210</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <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:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_71ee1f28a48b4912b7856878fffe6d71" contextRef="c20211231_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%; 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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6ca53082497a48cbbe21e6779f6c68de" contextRef="c20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,964,167</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <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:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_74e796cf373641daa869d8d47e0c4624" contextRef="c20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">32,668</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%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_e85b208449cd4a72aab42974aaa1fde6" contextRef="c20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,159,903</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_59bf2f8f2caf43f4b752ed6ec5430d19" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">771,737</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: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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:NetIncomeLoss" id="Fact_d9edf6248dc1424aafd3356543008867" contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember" 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:NetIncomeLoss" id="Fact_7dd7c1f845a045a090badfcc7ab6db76" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" 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:NetIncomeLoss" id="Fact_8c15f483d1064d24b2d9f6619420dd72" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" 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:NetIncomeLoss" id="Fact_166de7975ba34b89a10a2e6535435fbe" contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">65,165</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:NetIncomeLoss" id="Fact_e67dfd4b29294fe5a04362d945862f88" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">65,165</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized losses, net of tax</div></td>
    <td colspan="1" valign="bottom" 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>
    <td colspan="1" valign="bottom" 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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_ecabb894029043e0827e09799b634f83" contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember" 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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_1f8c2bf4d6034265bca78ef8f8152813" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" 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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_c252fecd225c4a61a39f2141313b069a" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">15,756</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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_b9c09de5a34f49b2bfc5a8e9efcba534" contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_76a2d72a1e7c4a8da884d26ad31c6802" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">15,756</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: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_06b5276b17cb47b2b6555023dab9cfec" contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember" 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_d95f53b4b13f443cbd0bc435f640800e" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_4995c8f2196140e6a69b1dc2b9a5305f" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">154</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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_7a87e7f86cba4eff8c9cf38cab460812" contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_3efe3a97b35e46be9a6cb637d571311c" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">154</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans</div></td>
    <td colspan="1" valign="bottom" 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:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_efb172d9a80a4f9c94cd3511ed3f16e9" contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">847</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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_8ac07b9c1fe44ba7983c69266299a134" contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_64beaae13e384dc7974a35c709224829" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,848</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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_7183dc09cfa54eea90ec50925a441ebc" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" 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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_28f6a3aee5dc49b0ae461653c0e378ce" contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_740610803a7b4e7ebd68ee69ac2c7e96" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,849</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: 28%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_9897ad26311f4f30a8d313ca1f6227c7" contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember" 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_7f83f4f9c68b46d5b1d2477f66dbe960" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,236</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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_93849307749e41309ff4147077bd45a2" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_a0e167b293a946898aabd539f2085050" contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_6705359364e94eb6a3a9944a3bf9888c" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,236</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: 28%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9.15pt; margin-left: 9.15pt; 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%; 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:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_0fd8bb9777ee47b3b343e25304e72e8f" contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">304</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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_b3a97b30724d4a72b0a88b1d62787ecf" contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember" 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_5fe03c80b03541ca9c3f81e124ca7bae" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,173</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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_cb8de3379f1d415b9a6c56f54a5ffe13" contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_b37f16c3895c4324a133db8ca300d70d" contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember" 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_c21be2c2b9c54fd48d9752d97f10618a" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,173</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at <span style="text-indent: 0pt;">March 31, 2022</span></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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_8f9f94f1d3d940a68541e958de1f55f0" contextRef="c20220331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:numdotdecimal">141,753</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_0fa1ab6fe60a48e88125f45695548614" contextRef="c20220331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">142</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_ba66578036484b5f968843707bc07ed1" contextRef="c20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,983,078</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_459e8dddf67049ffbc89a031afcfb160" contextRef="c20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">48,578</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_f3febeb396b8498887a5e227b0d9203b" contextRef="c20220331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">1,225,068</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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_410eb94491b24411ae562ce3bd42c127" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">709,574</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">6</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="CashFlows"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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" class="cfttable" 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; font-weight: bold;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">&#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: 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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:NetIncomeLoss" id="Fact_f7c36546ee144c2c86ebae7331367498" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">65,165</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:NetIncomeLoss" id="Fact_a21016941dc0429abc056d42872b32b2" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">89,869</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to reconcile net loss to net cash used in operating activities:</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>
  </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;">Depreciation</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:Depreciation" id="Fact_100d69cecae84cbdad6e81cc7ef52262" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,701</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:Depreciation" id="Fact_8c77ba4be59247e38c94131c141d0abf" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,917</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of right-of-use operating lease assets</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:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_9e6711269ac449af9f3ea5cf3d5eaa6a" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">602</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:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_5558af291e4642f9823614e737f072ce" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">394</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of patents</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_edc8ad178aa7466a8d83a15fca3ea881" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">592</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_f8039ed914974946804216d314447463" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">544</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of premium on investments, net</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_246d1c45e9574034a56b56918f85ebb2" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">4,175</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:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_4aaed7ae1baf412b9dbc761309827e6d" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">4,023</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of debt issuance costs</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_0996ae3cb47d4deda2a70a7fe98905e0" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,343</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_0c9f58357fb646578e9fa6d8e42f1be2" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">860</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,236</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:ShareBasedCompensation" id="Fact_75990e27c7ef4862aef11ff7e8db6961" 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>
  </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>
    <td colspan="1" valign="bottom" 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:RealizedInvestmentGainsLosses" id="Fact_14350362b48c4c63a2d02245c7bdfc8e" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">10</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:RealizedInvestmentGainsLosses" id="Fact_1d0b4f23d12a4c8d93769c2560a353b7" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">13</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash losses related to disposal of property, plant and equipment</div></td>
    <td colspan="1" valign="bottom" 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:GainLossOnDispositionOfAssets" id="Fact_01a5dec9e9674dcc9254b9bfa6e79949" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">527</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:GainLossOnDispositionOfAssets" id="Fact_9e5576dfce9c47598f395f576a1839a2" 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%; 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;">Non-cash losses related to patents</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_7fcd200b638b455db39131034fdc6876" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">110</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:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_fe5c9b55fb8549bebb24e58da0204a34" 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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Changes in operating assets and liabilities:</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>
  </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="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">35,774</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="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>
  </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;">Inventories</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:IncreaseDecreaseInInventories" id="Fact_6cc57db037e24224babb23341491fa27" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">774</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:IncreaseDecreaseInInventories" id="Fact_855e538885814931adc2c6ca522196ff" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">234</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: 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;">Other current and long-term assets</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherOperatingAssets" id="Fact_6beef6ad7156442b8b64be1683073767" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,222</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:IncreaseDecreaseInOtherOperatingAssets" id="Fact_6b1b789ac55944df81d7f4361d13837c" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">16,481</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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes receivable</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:IncreaseDecreaseInAccruedIncomeTaxesPayable" id="Fact_920199b2a9f34fa1848e6eca1d94d87b" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">865</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:IncreaseDecreaseInAccruedIncomeTaxesPayable" id="Fact_86237017148a4c7887a8ba1643288e88" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2</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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounts 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;">&#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:IncreaseDecreaseInAccountsPayable" id="Fact_8a994583ad564784b70d134601567caf" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,878</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:IncreaseDecreaseInAccountsPayable" id="Fact_7d0b289b5d31478faec7c1781df64a2b" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">9,569</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><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>
    <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:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_5f5c568dfefd46649d7f965b7bc2f695" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">22,285</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:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_e29dcd8047ff491884c92796c96013cb" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">36,465</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: 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>
    <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:IncreaseDecreaseInOtherCurrentLiabilities" id="Fact_08f6c9cf45f246f6a33cd0c9749cb737" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">10,473</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:IncreaseDecreaseInOtherCurrentLiabilities" id="Fact_8da87902979a47b2b8cd9fcda264eef6" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">11,905</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 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>
    <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:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_5d444769c22d417199294bd747e46936" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">25,018</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:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_7536a4e7a5c548658c9c6c4190e7e76b" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">23,717</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: 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="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">31,650</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:NetCashProvidedByUsedInOperatingActivities" id="Fact_aaaa638d546d45448755c94c63222ccd" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">54,662</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%;">&#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="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">462,855</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:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_50e0b935822448d399c6da50df573ca5" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">330,051</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: 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="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">178,837</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:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_6dc4fafd64864e3188177206b20e21e5" 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>
  </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>
    <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:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_5c4c86b4988a4bcc93f568312cf27532" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,705</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:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_23746708bcf2482183689f1b17ed01be" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,772</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: 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;">Acquisition of licenses and other assets, net</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:PaymentsToAcquireIntangibleAssets" id="Fact_bedfe0d50deb453aac9adee6a16b847b" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">826</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:PaymentsToAcquireIntangibleAssets" id="Fact_2503d109e9bf429abba6e180534abb50" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,228</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) provided by investing 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:NetCashProvidedByUsedInInvestingActivities" id="Fact_92cb4d2048d14989a03cc74060fe995e" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">287,549</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:NetCashProvidedByUsedInInvestingActivities" id="Fact_98c358a7d9cc4f7dbda064764db082d3" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">78,856</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;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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>
    <td colspan="1" valign="bottom" 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: 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>
    <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_ddb0c2b46432418f9be1b92d0e804ae9" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,848</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="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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><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%; 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:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_b75a3de029544b8ea1fafba1be80eb98" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,173</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:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_2013b605a8914f73b56ab03781e33c14" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,337</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: 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 financing 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:NetCashProvidedByUsedInFinancingActivities" id="Fact_eaaca3e288be4952adf9a7f8f7bf8f92" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">7,325</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:NetCashProvidedByUsedInFinancingActivities" id="Fact_af5d9d765265424f939925e68f5a2822" 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; 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%;">&#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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effects of exchange rates on cash</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:EffectOfExchangeRateOnCashAndCashEquivalents" id="Fact_05d7fd45bf434136a2b94742f2dddc94" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">154</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:EffectOfExchangeRateOnCashAndCashEquivalents" id="Fact_44c0dad63f8b413c8cf4e5c0bbc41200" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" sign="-" 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;"><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%;">&#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;">Net (decrease) increase in cash and cash equivalents</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:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_381c34e8f196433d88bcc5a40e6d5ead" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:numdotdecimal">326,678</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:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_695ef20670484629abffb58a97885612" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16,491</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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash and cash equivalents at beginning of period</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:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_f005ffe7399e4372b86484b39e4de899" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">869,191</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:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_6c5f411c5f5446ed84bf5042679097db" contextRef="c20201231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">397,664</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash and cash equivalents at end of period</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_22fc70baf81348a4bed7f3a0cca2d925" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">542,513</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_26348b07f1404eb2b971660219ce0e2f" contextRef="c20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">414,155</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: 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;">Supplemental disclosures of cash flow information:</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;">Interest paid</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:InterestPaidNet" id="Fact_1c0954c400a1482b8ec42df7704e2f57" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">594</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InterestPaidNet" id="Fact_99a9e46f9bbe4846a09670f406e934e7" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">594</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes paid</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:IncomeTaxesPaid" id="Fact_e1a1dc9fdd464c8d8c36512a7e6251fb" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2</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:IncomeTaxesPaid" id="Fact_85ce33dc7db749c6bac7ae7eadc1d4ee" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2</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%;">&#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;">Supplemental disclosures of non-cash investing and financing 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;">Amounts accrued for capital and patent expenditures</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="ions:NonCashCapitalAndPatentExpenditures" id="Fact_e747862ab08345fcae14d5a69abc90c7" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,344</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <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:NonCashCapitalAndPatentExpenditures" id="Fact_b758276d9ff04fe0a8e9a80dd38bfae6" contextRef="c20210101to20210331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,876</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">7</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Notes"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">NOTES TO 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, 2022</div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" id="Text_fa51a4329a644679a99132053d097cc9" contextRef="c20220101to20220331" escape="true" continuedAt="Text_41088a61c1b94f7989c6bffbedc3259d1">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; Basis of Presentation</div>
</ix:nonNumeric><ix:continuation id="Text_41088a61c1b94f7989c6bffbedc3259d1" continuedAt="Text_41088a61c1b94f7989c6bffbedc3259d2">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_41088a61c1b94f7989c6bffbedc3259d2" continuedAt="Text_41088a61c1b94f7989c6bffbedc3259d3"><ix:nonNumeric name="us-gaap:BasisOfAccountingPolicyPolicyTextBlock" id="Text_81b8305cf0914dd480c3779bb834c828" contextRef="c20220101to20220331" escape="true">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepared the unaudited interim condensed consolidated financial statements for the three months ended&#xA0;March 31, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. 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 December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_41088a61c1b94f7989c6bffbedc3259d3" continuedAt="Text_41088a61c1b94f7989c6bffbedc3259d4">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_41088a61c1b94f7989c6bffbedc3259d4"><ix:nonNumeric name="us-gaap:ConsolidationPolicyTextBlock" id="Text_c46fa5d2afe84cef91a6b400d35f4f37" contextRef="c20220101to20220331" escape="true">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our 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;).</div>
</ix:nonNumeric></ix:continuation></div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:SignificantAccountingPoliciesTextBlock" id="Text_3f631d62f8b3441ca8993f923978bb09" contextRef="c20220101to20220331" escape="true" continuedAt="Text_28567aedb1e54e849272ca632f6c101f1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2.&#160; Significant Accounting Policies</div>
</ix:nonNumeric><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f1" continuedAt="Text_28567aedb1e54e849272ca632f6c101f2">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f2" continuedAt="Text_28567aedb1e54e849272ca632f6c101f3"><ix:nonNumeric name="us-gaap:RevenueFromContractWithCustomerPolicyTextBlock" id="Text_23dcd0c53d73416a92d74f38fe21501a" contextRef="c20220101to20220331" escape="true" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c1">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f3" continuedAt="Text_28567aedb1e54e849272ca632f6c101f4"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c1" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f4" continuedAt="Text_28567aedb1e54e849272ca632f6c101f5"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c2" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c3">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f5" continuedAt="Text_28567aedb1e54e849272ca632f6c101f6"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c3" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c4">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f6" continuedAt="Text_28567aedb1e54e849272ca632f6c101f7"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c4" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c5">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f7" continuedAt="Text_28567aedb1e54e849272ca632f6c101f8"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c5" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c6">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f8" continuedAt="Text_28567aedb1e54e849272ca632f6c101f9"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c6" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c7">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. If there is no appropriate analogous authoritative accounting literature, ASC 808 suggests companies consistently apply a reasonable and rational accounting policy election. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f9" continuedAt="Text_28567aedb1e54e849272ca632f6c101f10"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c7" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c8">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f10" continuedAt="Text_28567aedb1e54e849272ca632f6c101f11"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c8" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c9">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f11" continuedAt="Text_28567aedb1e54e849272ca632f6c101f12"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c9" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c10">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f12" continuedAt="Text_28567aedb1e54e849272ca632f6c101f13"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c10" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c11">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f13" continuedAt="Text_28567aedb1e54e849272ca632f6c101f14"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c11" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c12">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f14" continuedAt="Text_28567aedb1e54e849272ca632f6c101f15"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c12" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c13">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f15" continuedAt="Text_28567aedb1e54e849272ca632f6c101f16"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c13" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c14">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f16" continuedAt="Text_28567aedb1e54e849272ca632f6c101f17"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c14" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c15">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f17" continuedAt="Text_28567aedb1e54e849272ca632f6c101f18"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c15" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c16">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f18" continuedAt="Text_28567aedb1e54e849272ca632f6c101f19"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c16" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c17">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.</div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">8</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f19" continuedAt="Text_28567aedb1e54e849272ca632f6c101f20"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c17" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c18">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f20" continuedAt="Text_28567aedb1e54e849272ca632f6c101f21"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c18" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c19">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f21" continuedAt="Text_28567aedb1e54e849272ca632f6c101f22"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c19" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c20">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f22" continuedAt="Text_28567aedb1e54e849272ca632f6c101f23"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c20" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c21">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f23" continuedAt="Text_28567aedb1e54e849272ca632f6c101f24"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c21" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c22">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f24" continuedAt="Text_28567aedb1e54e849272ca632f6c101f25"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c22" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c23">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f25" continuedAt="Text_28567aedb1e54e849272ca632f6c101f26"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c23" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c24">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f26" continuedAt="Text_28567aedb1e54e849272ca632f6c101f27"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c24" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c25">
<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 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for collaborations with substantive changes that occurred in 2022. 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, 2021 for a summary of each of our material collaborative agreements.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f27" continuedAt="Text_28567aedb1e54e849272ca632f6c101f28"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c25" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c26">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f28" continuedAt="Text_28567aedb1e54e849272ca632f6c101f29"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c26" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c27">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f29" continuedAt="Text_28567aedb1e54e849272ca632f6c101f30"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c27" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c28">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f30" continuedAt="Text_28567aedb1e54e849272ca632f6c101f31"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c28" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c29">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f31" continuedAt="Text_28567aedb1e54e849272ca632f6c101f32"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c29" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c30">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f32" continuedAt="Text_28567aedb1e54e849272ca632f6c101f33"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c30" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c31">
<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">
  <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; 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>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f33" continuedAt="Text_28567aedb1e54e849272ca632f6c101f34"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c31" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c32">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f34" continuedAt="Text_28567aedb1e54e849272ca632f6c101f35"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c32" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c33">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f35" continuedAt="Text_28567aedb1e54e849272ca632f6c101f36"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c33" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c34">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f36" continuedAt="Text_28567aedb1e54e849272ca632f6c101f37"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c34" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c35">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partner approved the contract and we are both committed to perform our obligations;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f37" continuedAt="Text_28567aedb1e54e849272ca632f6c101f38"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c35" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c36">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f38" continuedAt="Text_28567aedb1e54e849272ca632f6c101f39"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c36" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c37">
<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">
  <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;">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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f39" continuedAt="Text_28567aedb1e54e849272ca632f6c101f40"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c37" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c38">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe collectability of the consideration is probable.</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f40" continuedAt="Text_28567aedb1e54e849272ca632f6c101f41"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c38" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c39">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f41" continuedAt="Text_28567aedb1e54e849272ca632f6c101f42"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c39" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c40">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f42" continuedAt="Text_28567aedb1e54e849272ca632f6c101f43"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c40" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c41">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f43" continuedAt="Text_28567aedb1e54e849272ca632f6c101f44"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c41" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c42">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f44" continuedAt="Text_28567aedb1e54e849272ca632f6c101f45"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c42" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c43">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f45" continuedAt="Text_28567aedb1e54e849272ca632f6c101f46"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c43" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c44">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f46" continuedAt="Text_28567aedb1e54e849272ca632f6c101f47"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c44" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c45">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f47" continuedAt="Text_28567aedb1e54e849272ca632f6c101f48"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c45" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c46">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f48" continuedAt="Text_28567aedb1e54e849272ca632f6c101f49"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c46" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c47">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f49" continuedAt="Text_28567aedb1e54e849272ca632f6c101f50"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c47" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c48">
<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">
  <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; 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f50" continuedAt="Text_28567aedb1e54e849272ca632f6c101f51"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c48" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c49">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f51" continuedAt="Text_28567aedb1e54e849272ca632f6c101f52"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c49" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c50">
<div 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>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">9</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f52" continuedAt="Text_28567aedb1e54e849272ca632f6c101f53"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c50" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c51">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f53" continuedAt="Text_28567aedb1e54e849272ca632f6c101f54"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c51" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c52">
<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 first quarter of 2022, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c66a5241a21143ed8f3a497ac21b877d" contextRef="c20220101to20220331_ProductOrServiceAxis_Ion859Member" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#8217;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f54" continuedAt="Text_28567aedb1e54e849272ca632f6c101f55"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c52" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c53">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f55" continuedAt="Text_28567aedb1e54e849272ca632f6c101f56"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c53" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c54">
<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">
  <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; 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f56" continuedAt="Text_28567aedb1e54e849272ca632f6c101f57"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c54" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c55">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f57" continuedAt="Text_28567aedb1e54e849272ca632f6c101f58"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c55" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c56">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f58" continuedAt="Text_28567aedb1e54e849272ca632f6c101f59"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c56" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c57">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f59" continuedAt="Text_28567aedb1e54e849272ca632f6c101f60"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c57" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c58">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f60" continuedAt="Text_28567aedb1e54e849272ca632f6c101f61"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c58" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c59">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f61" continuedAt="Text_28567aedb1e54e849272ca632f6c101f62"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c59" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c60">
<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">
  <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;">Estimated future product sales;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f62" continuedAt="Text_28567aedb1e54e849272ca632f6c101f63"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c60" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c61">
<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">
  <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;">Estimated royalties we may receive from future product sales;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f63" continuedAt="Text_28567aedb1e54e849272ca632f6c101f64"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c61" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c62">
<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">
  <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;">Estimated contractual milestone payments we may receive;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f64" continuedAt="Text_28567aedb1e54e849272ca632f6c101f65"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c62" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c63">
<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">
  <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;">Estimated expenses we may incur;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f65" continuedAt="Text_28567aedb1e54e849272ca632f6c101f66"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c63" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c64">
<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">
  <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;">Estimated income taxes; and</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f66" continuedAt="Text_28567aedb1e54e849272ca632f6c101f67"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c64" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c65">
<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">
  <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;">A discount rate.</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f67" continuedAt="Text_28567aedb1e54e849272ca632f6c101f68"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c65" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c66">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f68" continuedAt="Text_28567aedb1e54e849272ca632f6c101f69"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c66" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c67">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f69" continuedAt="Text_28567aedb1e54e849272ca632f6c101f70"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c67" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c68">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f70" continuedAt="Text_28567aedb1e54e849272ca632f6c101f71"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c68" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c69">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated number of internal hours we will spend performing these services;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f71" continuedAt="Text_28567aedb1e54e849272ca632f6c101f72"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c69" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c70">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work we will perform;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f72" continuedAt="Text_28567aedb1e54e849272ca632f6c101f73"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c70" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c71">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work that we will contract with third parties to perform; and</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f73" continuedAt="Text_28567aedb1e54e849272ca632f6c101f74"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c71" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c72">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of API we will use.</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f74" continuedAt="Text_28567aedb1e54e849272ca632f6c101f75"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c72" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c73">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f75" continuedAt="Text_28567aedb1e54e849272ca632f6c101f76"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c73" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c74">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f76" continuedAt="Text_28567aedb1e54e849272ca632f6c101f77"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c74" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c75">
<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f77" continuedAt="Text_28567aedb1e54e849272ca632f6c101f78"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c75" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c76">
<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">
  <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; 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f78" continuedAt="Text_28567aedb1e54e849272ca632f6c101f79"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c76" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c77">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f79" continuedAt="Text_28567aedb1e54e849272ca632f6c101f80"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c77" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c78">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f80" continuedAt="Text_28567aedb1e54e849272ca632f6c101f81"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c78" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c79">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f81" continuedAt="Text_28567aedb1e54e849272ca632f6c101f82"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c79" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c80">
<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>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">10</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f82" continuedAt="Text_28567aedb1e54e849272ca632f6c101f83"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c80" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c81">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f83" continuedAt="Text_28567aedb1e54e849272ca632f6c101f84"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c81" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c82">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are examples of when we typically recognize revenue based on the types of payments we receive.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f84" continuedAt="Text_28567aedb1e54e849272ca632f6c101f85"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c82" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c83">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f85" continuedAt="Text_28567aedb1e54e849272ca632f6c101f86"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c83" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c84">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f86" continuedAt="Text_28567aedb1e54e849272ca632f6c101f87"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c84" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c85">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f87" continuedAt="Text_28567aedb1e54e849272ca632f6c101f88"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c85" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c86">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f88" continuedAt="Text_28567aedb1e54e849272ca632f6c101f89"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c86" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c87">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f89" continuedAt="Text_28567aedb1e54e849272ca632f6c101f90"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c87" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c88">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f90" continuedAt="Text_28567aedb1e54e849272ca632f6c101f91"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c88" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c89">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f91" continuedAt="Text_28567aedb1e54e849272ca632f6c101f92"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c89" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c90">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f92" continuedAt="Text_28567aedb1e54e849272ca632f6c101f93"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c90" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c91">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f93" continuedAt="Text_28567aedb1e54e849272ca632f6c101f94"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c91" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c92">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f94" continuedAt="Text_28567aedb1e54e849272ca632f6c101f95"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c92" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c93">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f95" continuedAt="Text_28567aedb1e54e849272ca632f6c101f96"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c93" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c94">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f96" continuedAt="Text_28567aedb1e54e849272ca632f6c101f97"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c94" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c95">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f97" continuedAt="Text_28567aedb1e54e849272ca632f6c101f98"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c95" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c96">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f98" continuedAt="Text_28567aedb1e54e849272ca632f6c101f99"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c96" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c97">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f99" continuedAt="Text_28567aedb1e54e849272ca632f6c101f100"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c97" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c98">
<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 agreements 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. Under our agreements with Sobi, we transferred all reserves to Sobi. 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, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f100" continuedAt="Text_28567aedb1e54e849272ca632f6c101f101"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c98" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c99">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f101" continuedAt="Text_28567aedb1e54e849272ca632f6c101f102"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c99" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c100">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f102" continuedAt="Text_28567aedb1e54e849272ca632f6c101f103"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c100" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c101">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f103" continuedAt="Text_28567aedb1e54e849272ca632f6c101f104"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c101" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c102">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f104" continuedAt="Text_28567aedb1e54e849272ca632f6c101f105"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c102" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c103">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f105" continuedAt="Text_28567aedb1e54e849272ca632f6c101f106"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c103" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c104">
<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 and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. 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_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" 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_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" 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>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">11</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f106" continuedAt="Text_28567aedb1e54e849272ca632f6c101f107"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c104" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c105">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f107" continuedAt="Text_28567aedb1e54e849272ca632f6c101f108"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c105" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c106">
<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;">Milestone payments</span></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f108" continuedAt="Text_28567aedb1e54e849272ca632f6c101f109"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c106" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c107">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f109" continuedAt="Text_28567aedb1e54e849272ca632f6c101f110"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c107" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c108">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f110" continuedAt="Text_28567aedb1e54e849272ca632f6c101f111"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c108" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c109">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f111" continuedAt="Text_28567aedb1e54e849272ca632f6c101f112"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c109" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c110">
<div 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 2021, we achieved a $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPriceAdditions" id="Fact_4419a9d643c14dde9c2d40f4d61b0e4c" contextRef="c20211001to20211231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f112" continuedAt="Text_28567aedb1e54e849272ca632f6c101f113"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c110" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c111">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f113" continuedAt="Text_28567aedb1e54e849272ca632f6c101f114"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c111" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c112">
<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 first quarter of 2022, we recognized $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_94ca715aaad045a79c4d7f4d005942f7" contextRef="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">18</ix:nonFraction> million in milestone payments when Biogen advanced <ix:nonFraction name="ions:NumberOfTargetsAdvanced" id="Fact_f2258c9c40f845b4bb100ba3ef3051b5" contextRef="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> targets under our 2013 strategic collaboration. 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 first quarter of 2022.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f114" continuedAt="Text_28567aedb1e54e849272ca632f6c101f115"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c112" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c113">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f115" continuedAt="Text_28567aedb1e54e849272ca632f6c101f116"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c113" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c114">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f116" continuedAt="Text_28567aedb1e54e849272ca632f6c101f117"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c114" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c115">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f117" continuedAt="Text_28567aedb1e54e849272ca632f6c101f118"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c115" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c116">
<div 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 2021, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_13676dd08f854acb99df553544328759" contextRef="c20211001to20211231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">60</ix:nonFraction> million license fee from Biogen when Biogen licensed ION306, an investigational medicine in development to treat SMA.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f118" continuedAt="Text_28567aedb1e54e849272ca632f6c101f119"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c116" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c117">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f119" continuedAt="Text_28567aedb1e54e849272ca632f6c101f120"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c117" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c118">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f120" continuedAt="Text_28567aedb1e54e849272ca632f6c101f121"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c118" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c119">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f121" continuedAt="Text_28567aedb1e54e849272ca632f6c101f122"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c119" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c120">
<div 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. For example, in the fourth quarter of 2020, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d95ecd0c2d0e4ea494c6592f2153d064" contextRef="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">41.2</ix:nonFraction> million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f122" continuedAt="Text_28567aedb1e54e849272ca632f6c101f123"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c120" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c121">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f123" continuedAt="Text_28567aedb1e54e849272ca632f6c101f124"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c121" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c122">
<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;">Amendments to Agreements</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f124" continuedAt="Text_28567aedb1e54e849272ca632f6c101f125"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c122" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c123">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f125" continuedAt="Text_28567aedb1e54e849272ca632f6c101f126"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c123" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c124">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f126" continuedAt="Text_28567aedb1e54e849272ca632f6c101f127"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c124" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c125">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f127" continuedAt="Text_28567aedb1e54e849272ca632f6c101f128"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c125" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c126">
<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">
  <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;">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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f128" continuedAt="Text_28567aedb1e54e849272ca632f6c101f129"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c126" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c127">
<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">
  <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;">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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f129" continuedAt="Text_28567aedb1e54e849272ca632f6c101f130"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c127" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c128">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f130" continuedAt="Text_28567aedb1e54e849272ca632f6c101f131"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c128" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c129">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f131" continuedAt="Text_28567aedb1e54e849272ca632f6c101f132"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c129" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c130">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f132" continuedAt="Text_28567aedb1e54e849272ca632f6c101f133"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c130" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c131">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Multiple agreements</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f133" continuedAt="Text_28567aedb1e54e849272ca632f6c101f134"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c131" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c132">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f134" continuedAt="Text_28567aedb1e54e849272ca632f6c101f135"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c132" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c133">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f135" continuedAt="Text_28567aedb1e54e849272ca632f6c101f136"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c133" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c134">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f136" continuedAt="Text_28567aedb1e54e849272ca632f6c101f137"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c134" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c135">
<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">
  <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;">Whether the agreements were negotiated together with a single objective;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f137" continuedAt="Text_28567aedb1e54e849272ca632f6c101f138"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c135" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c136">
<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">
  <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;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f138" continuedAt="Text_28567aedb1e54e849272ca632f6c101f139"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c136" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c137">
<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">
  <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;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">12</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f139" continuedAt="Text_28567aedb1e54e849272ca632f6c101f140"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c137" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c138">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f140" continuedAt="Text_28567aedb1e54e849272ca632f6c101f141"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c138" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c139">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f141" continuedAt="Text_28567aedb1e54e849272ca632f6c101f142"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c139" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c140">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f142" continuedAt="Text_28567aedb1e54e849272ca632f6c101f143"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c140" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c141">
<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 <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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f143" continuedAt="Text_28567aedb1e54e849272ca632f6c101f144"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c141" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c142">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f144" continuedAt="Text_28567aedb1e54e849272ca632f6c101f145"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c142" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c143">
<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;">Eplontersen Collaboration with AstraZeneca</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f145" continuedAt="Text_28567aedb1e54e849272ca632f6c101f146"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c143" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c144">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f146" continuedAt="Text_28567aedb1e54e849272ca632f6c101f147"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c144" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c145">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_53da6e65fb0741c483420c0238104ade" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">200</ix:nonFraction> million upfront payment in 2021.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f147" continuedAt="Text_28567aedb1e54e849272ca632f6c101f148"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c145" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c146">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f148" continuedAt="Text_28567aedb1e54e849272ca632f6c101f149"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c146" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c147">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_b27e54c14e90416580647f971d492180" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f149" continuedAt="Text_28567aedb1e54e849272ca632f6c101f150"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c147" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c148">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f150" continuedAt="Text_28567aedb1e54e849272ca632f6c101f151"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c148" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c149">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_e8e1aec533f84dbf98a2133cce0f7dc7" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_387a94400e2542adb3feef5e16cbd22c" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">200</ix:nonFraction> million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f151" continuedAt="Text_28567aedb1e54e849272ca632f6c101f152"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c149" continuedAt="Text_75ec27f985a04fa38da4d5f96138bf6c150">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f152" continuedAt="Text_28567aedb1e54e849272ca632f6c101f153"><ix:continuation id="Text_75ec27f985a04fa38da4d5f96138bf6c150">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for <ix:nonFraction name="ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="Fact_3165c6664dcc46f6bd3fb9a729593495" contextRef="c20220101to20220331_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">55</ix:nonFraction> percent of the costs associated with the ongoing global Phase 3 development program. As we continue to lead the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively. Refer to Item 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations</span>, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. </div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f153" continuedAt="Text_28567aedb1e54e849272ca632f6c101f154">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f154" continuedAt="Text_28567aedb1e54e849272ca632f6c101f155"><ix:nonNumeric name="us-gaap:ReceivablesPolicyTextBlock" id="Text_65525657713c48478f6f26b531ff73b7" contextRef="c20220101to20220331" escape="true" continuedAt="Text_444f4f3bb6014f2b85bf74a42e33909c1">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f155" continuedAt="Text_28567aedb1e54e849272ca632f6c101f156"><ix:continuation id="Text_444f4f3bb6014f2b85bf74a42e33909c1" continuedAt="Text_444f4f3bb6014f2b85bf74a42e33909c2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f156" continuedAt="Text_28567aedb1e54e849272ca632f6c101f157"><ix:continuation id="Text_444f4f3bb6014f2b85bf74a42e33909c2" continuedAt="Text_444f4f3bb6014f2b85bf74a42e33909c3">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f157" continuedAt="Text_28567aedb1e54e849272ca632f6c101f158"><ix:continuation id="Text_444f4f3bb6014f2b85bf74a42e33909c3" continuedAt="Text_444f4f3bb6014f2b85bf74a42e33909c4">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f158" continuedAt="Text_28567aedb1e54e849272ca632f6c101f159"><ix:continuation id="Text_444f4f3bb6014f2b85bf74a42e33909c4">
<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, 2022, approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_ddb9c9779caa4c7ba7a8628627b81f91" contextRef="c20220101to20220331_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">82.2</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_1a88c8e3635d4a64afd7542090bb8bb4" contextRef="c20220101to20220331" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> significant customers. As of December 31, 2021, approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_2797753f496a4c3a9e250ecbc9db8bec" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">93.8</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_61c499808edf4f65970284a4fd7b4782" contextRef="c20210101to20211231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> significant customers.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f159" continuedAt="Text_28567aedb1e54e849272ca632f6c101f160">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f160" continuedAt="Text_28567aedb1e54e849272ca632f6c101f161"><ix:nonNumeric name="us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" id="Text_6f3107eba95140ffb1c98fd3296491db" contextRef="c20220101to20220331" escape="true" continuedAt="Text_3af08da370d440c392259ced17c1b3621">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f161" continuedAt="Text_28567aedb1e54e849272ca632f6c101f162"><ix:continuation id="Text_3af08da370d440c392259ced17c1b3621" continuedAt="Text_3af08da370d440c392259ced17c1b3622">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f162" continuedAt="Text_28567aedb1e54e849272ca632f6c101f163"><ix:continuation id="Text_3af08da370d440c392259ced17c1b3622">
<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>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">13</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f163" continuedAt="Text_28567aedb1e54e849272ca632f6c101f164">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f164" continuedAt="Text_28567aedb1e54e849272ca632f6c101f165"><ix:nonNumeric name="us-gaap:RevenueRecognitionPolicyTextBlock" id="Text_1fffd2b34a31436fa2700206d4f2a54a" contextRef="c20220101to20220331" escape="true" continuedAt="Text_1807a186786940c3a4fef403d5b101ed1">
<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;">Deferred Revenue</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f165" continuedAt="Text_28567aedb1e54e849272ca632f6c101f166"><ix:continuation id="Text_1807a186786940c3a4fef403d5b101ed1" continuedAt="Text_1807a186786940c3a4fef403d5b101ed2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f166" continuedAt="Text_28567aedb1e54e849272ca632f6c101f167"><ix:continuation id="Text_1807a186786940c3a4fef403d5b101ed2">
<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&#xA0;March 31, 2022 and 2021, we recognized $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_29a96e3cb4bb4440a9a1b2cd97733561" contextRef="c20220101to20220331" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">26.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_9b7323eabb394f1aa269712264f74431" contextRef="c20210101to20210331" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">26.0</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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f167" continuedAt="Text_28567aedb1e54e849272ca632f6c101f168">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f168" continuedAt="Text_28567aedb1e54e849272ca632f6c101f169"><ix:nonNumeric name="us-gaap:CostOfSalesPolicyTextBlock" id="Text_a7157f5414bc403797c3de4182f78f4f" contextRef="c20220101to20220331" escape="true" continuedAt="Text_d8d64a88687d44a48c9305c233037bb31">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f169" continuedAt="Text_28567aedb1e54e849272ca632f6c101f170"><ix:continuation id="Text_d8d64a88687d44a48c9305c233037bb31" continuedAt="Text_d8d64a88687d44a48c9305c233037bb32">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f170" continuedAt="Text_28567aedb1e54e849272ca632f6c101f171"><ix:continuation id="Text_d8d64a88687d44a48c9305c233037bb32">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f171" continuedAt="Text_28567aedb1e54e849272ca632f6c101f172">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f172" continuedAt="Text_28567aedb1e54e849272ca632f6c101f173"><ix:nonNumeric name="us-gaap:InvestmentPolicyTextBlock" id="Text_2be3f3248a3e4b9897806424f39c50c5" contextRef="c20220101to20220331" escape="true" continuedAt="Text_e2522bbd983e4afea77d297e8d2e35441">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f173" continuedAt="Text_28567aedb1e54e849272ca632f6c101f174"><ix:continuation id="Text_e2522bbd983e4afea77d297e8d2e35441" continuedAt="Text_e2522bbd983e4afea77d297e8d2e35442">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f174" continuedAt="Text_28567aedb1e54e849272ca632f6c101f175"><ix:continuation id="Text_e2522bbd983e4afea77d297e8d2e35442" continuedAt="Text_e2522bbd983e4afea77d297e8d2e35443">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f175" continuedAt="Text_28567aedb1e54e849272ca632f6c101f176"><ix:continuation id="Text_e2522bbd983e4afea77d297e8d2e35443" continuedAt="Text_e2522bbd983e4afea77d297e8d2e35444">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f176" continuedAt="Text_28567aedb1e54e849272ca632f6c101f177"><ix:continuation id="Text_e2522bbd983e4afea77d297e8d2e35444" continuedAt="Text_e2522bbd983e4afea77d297e8d2e35445">
<div 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, 2022, we held equity investments in <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8037e90f29fb43ae9797ff009a688387" contextRef="c20220331" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> publicly held companies, Antisense Therapeutics Limited, or ATL, Bicycle Therapeutics plc, or Bicycle, and ProQR Therapeutics N.V., or ProQR. We also held equity investments in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_e003aeab75174162b833cf14b3a44106" contextRef="c20220331" unitRef="U010" 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, YourBio Health, Inc. (formerly Seventh Sense Biosystems) and Suzhou-Ribo Life Science Co, Ltd.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f177" continuedAt="Text_28567aedb1e54e849272ca632f6c101f178"><ix:continuation id="Text_e2522bbd983e4afea77d297e8d2e35445" continuedAt="Text_e2522bbd983e4afea77d297e8d2e35446">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f178" continuedAt="Text_28567aedb1e54e849272ca632f6c101f179"><ix:continuation id="Text_e2522bbd983e4afea77d297e8d2e35446">
<div 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 2020, we revalued our investments in <ix:nonFraction name="ions:NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" id="Fact_1d052d9ce42e45d89c9a5e9b00144f66" contextRef="c20200101to20201231" unitRef="U011" 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. As a result of these observable price changes, we recognized a total gain of $<ix:nonFraction name="us-gaap:GainLossOnInvestments" id="Fact_e09e9575233b4dcfb1b480c449770f50" contextRef="c20200101to20201231_FinancialInstrumentAxis_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">14.8</ix:nonFraction> million on our investments in these companies in our condensed consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f179" continuedAt="Text_28567aedb1e54e849272ca632f6c101f180">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f180" continuedAt="Text_28567aedb1e54e849272ca632f6c101f181"><ix:nonNumeric name="us-gaap:InventoryPolicyTextBlock" id="Text_7383a8eea0944a5fa271be67a4f6a1f6" contextRef="c20220101to20220331" escape="true" continuedAt="Text_3fa89efe69074d3a8f100b8a6876c22e1">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f181" continuedAt="Text_28567aedb1e54e849272ca632f6c101f182"><ix:continuation id="Text_3fa89efe69074d3a8f100b8a6876c22e1" continuedAt="Text_3fa89efe69074d3a8f100b8a6876c22e2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f182" continuedAt="Text_28567aedb1e54e849272ca632f6c101f183"><ix:continuation id="Text_3fa89efe69074d3a8f100b8a6876c22e2" continuedAt="Text_3fa89efe69074d3a8f100b8a6876c22e3">
<div 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. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f183" continuedAt="Text_28567aedb1e54e849272ca632f6c101f184"><ix:continuation id="Text_3fa89efe69074d3a8f100b8a6876c22e3" continuedAt="Text_3fa89efe69074d3a8f100b8a6876c22e4">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f184" continuedAt="Text_28567aedb1e54e849272ca632f6c101f185"><ix:continuation id="Text_3fa89efe69074d3a8f100b8a6876c22e4" continuedAt="Text_3fa89efe69074d3a8f100b8a6876c22e5">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We recorded an immaterial amount of inventory write-offs for the three months ended&#xA0;March 31, 2022 and 2021.</div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">14</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f185" continuedAt="Text_28567aedb1e54e849272ca632f6c101f186"><ix:continuation id="Text_3fa89efe69074d3a8f100b8a6876c22e5" continuedAt="Text_3fa89efe69074d3a8f100b8a6876c22e6">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f186" continuedAt="Text_28567aedb1e54e849272ca632f6c101f187"><ix:continuation id="Text_3fa89efe69074d3a8f100b8a6876c22e6" continuedAt="Text_3fa89efe69074d3a8f100b8a6876c22e7"><ix:nonNumeric name="us-gaap:ScheduleOfInventoryCurrentTableTextBlock" id="Text_36cd1b45dfff4b728da90ffcc303bb51" contextRef="c20220101to20220331" escape="true" continuedAt="Text_395a4465ba444d2895ece93c4dcc4dd51">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>
</ix:nonNumeric></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f187" continuedAt="Text_28567aedb1e54e849272ca632f6c101f188"><ix:continuation id="Text_3fa89efe69074d3a8f100b8a6876c22e7" continuedAt="Text_3fa89efe69074d3a8f100b8a6876c22e8"><ix:continuation id="Text_395a4465ba444d2895ece93c4dcc4dd51" continuedAt="Text_395a4465ba444d2895ece93c4dcc4dd52">
<div><br /></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f188" continuedAt="Text_28567aedb1e54e849272ca632f6c101f189"><ix:continuation id="Text_3fa89efe69074d3a8f100b8a6876c22e8"><ix:continuation id="Text_395a4465ba444d2895ece93c4dcc4dd52">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2022</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;">December 31, 2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</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: 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" valign="bottom" style="vertical-align: bottom; 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:InventoryRawMaterials" id="Fact_3043726b7f0d40479abbe8c68900b93f" contextRef="c20220331_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,764</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:InventoryRawMaterials" id="Fact_6cec13c5f4334a1ba6216a6bc406747c" contextRef="c20211231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,507</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- commercial</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:InventoryRawMaterials" id="Fact_4a8280762bb1470eace824e402d6b623" contextRef="c20220331_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,165</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:InventoryRawMaterials" id="Fact_cf1accaf2b004921b424e5cd65e40c1f" contextRef="c20211231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,139</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</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:InventoryRawMaterials" id="Fact_9975fb0b2fa74f9e8ab81ebad8fb2237" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">17,929</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:InventoryRawMaterials" id="Fact_e3f1efde1cdb414796dec720e17eac54" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,646</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: 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" valign="bottom" 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:InventoryWorkInProcess" id="Fact_e7c4b729eb5c4047a12ddaf1f657b647" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,637</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:InventoryWorkInProcess" id="Fact_182d548d120f4e1daae74044c3e1bbe5" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,770</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%; 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>
    <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:InventoryFinishedGoods" id="Fact_b21c128f10e14f89b4963ecd92676ea1" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">466</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:InventoryFinishedGoods" id="Fact_70a3a016ecb849cd9021230823cf224d" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">390</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: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</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:InventoryNet" id="Fact_6f6a7ebaae1b4d95ace7fcfcf1fba210" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,032</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:InventoryNet" id="Fact_3e4c02edf53745679ae7e698216e7837" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24,806</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f189" continuedAt="Text_28567aedb1e54e849272ca632f6c101f190">
<div style="text-align: left;"><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f190" continuedAt="Text_28567aedb1e54e849272ca632f6c101f191"><ix:nonNumeric name="us-gaap:LesseeLeasesPolicyTextBlock" id="Text_e6ea38e98e2c41b6b3353d330002d1c3" contextRef="c20220101to20220331" escape="true" continuedAt="Text_548653592e634faa83bdd000c9990aff1">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f191" continuedAt="Text_28567aedb1e54e849272ca632f6c101f192"><ix:continuation id="Text_548653592e634faa83bdd000c9990aff1" continuedAt="Text_548653592e634faa83bdd000c9990aff2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f192" continuedAt="Text_28567aedb1e54e849272ca632f6c101f193"><ix:continuation id="Text_548653592e634faa83bdd000c9990aff2" continuedAt="Text_548653592e634faa83bdd000c9990aff3">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f193" continuedAt="Text_28567aedb1e54e849272ca632f6c101f194"><ix:continuation id="Text_548653592e634faa83bdd000c9990aff3" continuedAt="Text_548653592e634faa83bdd000c9990aff4">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f194" continuedAt="Text_28567aedb1e54e849272ca632f6c101f195"><ix:continuation id="Text_548653592e634faa83bdd000c9990aff4" continuedAt="Text_548653592e634faa83bdd000c9990aff5">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f195" continuedAt="Text_28567aedb1e54e849272ca632f6c101f196"><ix:continuation id="Text_548653592e634faa83bdd000c9990aff5" continuedAt="Text_548653592e634faa83bdd000c9990aff6">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f196" continuedAt="Text_28567aedb1e54e849272ca632f6c101f197"><ix:continuation id="Text_548653592e634faa83bdd000c9990aff6">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a <ix:nonNumeric name="ions:LesseeOperatingLeaseFreeRentPeriod" id="Fact_47d0951dc5cf46abb2ab61b44a977bad" contextRef="c20220101to20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember" format="ixt-sec:durwordsen">seven-month</ix:nonNumeric> free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $<ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue" id="Fact_6e9e11d907a042dcbbbf9300319016c9" contextRef="c20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">9.6</ix:nonFraction> million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f197" continuedAt="Text_28567aedb1e54e849272ca632f6c101f198">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f198" continuedAt="Text_28567aedb1e54e849272ca632f6c101f199">
<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>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f199" continuedAt="Text_28567aedb1e54e849272ca632f6c101f200">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f200" continuedAt="Text_28567aedb1e54e849272ca632f6c101f201"><ix:nonNumeric name="us-gaap:ResearchAndDevelopmentExpensePolicy" id="Text_d2e79a616c5149af971d3c0c1c8a1bfb" contextRef="c20220101to20220331" escape="true">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f201" continuedAt="Text_28567aedb1e54e849272ca632f6c101f202">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f202" continuedAt="Text_28567aedb1e54e849272ca632f6c101f203"><ix:nonNumeric name="us-gaap:IntangibleAssetsFiniteLivedPolicy" id="Text_eae0e633d40249c1b8d1ca3267edd5ca" contextRef="c20220101to20220331" escape="true">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f203" continuedAt="Text_28567aedb1e54e849272ca632f6c101f204">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f204" continuedAt="Text_28567aedb1e54e849272ca632f6c101f205"><ix:nonNumeric name="us-gaap:IncomeTaxPolicyTextBlock" id="Text_f07117ba6b154c219bc9ea7670cbc326" contextRef="c20220101to20220331" escape="true" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc91">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f205" continuedAt="Text_28567aedb1e54e849272ca632f6c101f206"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc91" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc92">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f206" continuedAt="Text_28567aedb1e54e849272ca632f6c101f207"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc92" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc93">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">15</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f207" continuedAt="Text_28567aedb1e54e849272ca632f6c101f208"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc93" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc94">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f208" continuedAt="Text_28567aedb1e54e849272ca632f6c101f209"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc94" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc95">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f209" continuedAt="Text_28567aedb1e54e849272ca632f6c101f210"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc95" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc96">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f210" continuedAt="Text_28567aedb1e54e849272ca632f6c101f211"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc96" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc97">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f211" continuedAt="Text_28567aedb1e54e849272ca632f6c101f212"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc97" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc98">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f212" continuedAt="Text_28567aedb1e54e849272ca632f6c101f213"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc98" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc99">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f213" continuedAt="Text_28567aedb1e54e849272ca632f6c101f214"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc99" continuedAt="Text_05eb9c325b644ad7af4682ec358cccc910">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f214" continuedAt="Text_28567aedb1e54e849272ca632f6c101f215"><ix:continuation id="Text_05eb9c325b644ad7af4682ec358cccc910">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f215" continuedAt="Text_28567aedb1e54e849272ca632f6c101f216">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f216" continuedAt="Text_28567aedb1e54e849272ca632f6c101f217"><ix:nonNumeric name="us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" id="Text_f326f7d8eff14d82bfdd56e71f4064a7" contextRef="c20220101to20220331" escape="true" continuedAt="Text_60c0ce656527489c9e931b76299a019f1">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f217" continuedAt="Text_28567aedb1e54e849272ca632f6c101f218"><ix:continuation id="Text_60c0ce656527489c9e931b76299a019f1" continuedAt="Text_60c0ce656527489c9e931b76299a019f2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f218" continuedAt="Text_28567aedb1e54e849272ca632f6c101f219"><ix:continuation id="Text_60c0ce656527489c9e931b76299a019f2">
<div 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f219" continuedAt="Text_28567aedb1e54e849272ca632f6c101f220">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f220" continuedAt="Text_28567aedb1e54e849272ca632f6c101f221"><ix:nonNumeric name="us-gaap:UseOfEstimates" id="Text_1b675f2ad8574bcb81c03f729eba4aa0" contextRef="c20220101to20220331" escape="true" continuedAt="Text_7fc1cfd097874dc88aa97b45a0a27f951">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f221" continuedAt="Text_28567aedb1e54e849272ca632f6c101f222"><ix:continuation id="Text_7fc1cfd097874dc88aa97b45a0a27f951" continuedAt="Text_7fc1cfd097874dc88aa97b45a0a27f952">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f222" continuedAt="Text_28567aedb1e54e849272ca632f6c101f223"><ix:continuation id="Text_7fc1cfd097874dc88aa97b45a0a27f952">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f223" continuedAt="Text_28567aedb1e54e849272ca632f6c101f224">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f224" continuedAt="Text_28567aedb1e54e849272ca632f6c101f225"><ix:nonNumeric name="us-gaap:EarningsPerSharePolicyTextBlock" id="Text_d8ae7016e11e44938c278329c28c5334" contextRef="c20220101to20220331" escape="true" continuedAt="Text_95c976a2eec04e9289aa18116e6515c51">
<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;">Basic and Diluted Net Loss Per Share</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f225" continuedAt="Text_28567aedb1e54e849272ca632f6c101f226"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c51" continuedAt="Text_95c976a2eec04e9289aa18116e6515c52">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f226" continuedAt="Text_28567aedb1e54e849272ca632f6c101f227"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c52" continuedAt="Text_95c976a2eec04e9289aa18116e6515c53">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f227" continuedAt="Text_28567aedb1e54e849272ca632f6c101f228"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c53" continuedAt="Text_95c976a2eec04e9289aa18116e6515c54">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f228" continuedAt="Text_28567aedb1e54e849272ca632f6c101f229"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c54" continuedAt="Text_95c976a2eec04e9289aa18116e6515c55">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the three months ended&#xA0;March 31, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended March 31, 2022 and 2021 were $<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_aab817918ee7462eafc4e0247e0ea5c8" contextRef="c20220101to20220331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.46</ix:nonFraction> and $<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_58043c7336904e8090a7cbe86199682a" contextRef="c20210101to20210331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:numdotdecimal">0.64</ix:nonFraction>, respectively.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f229" continuedAt="Text_28567aedb1e54e849272ca632f6c101f230"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c55" continuedAt="Text_95c976a2eec04e9289aa18116e6515c56">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f230" continuedAt="Text_28567aedb1e54e849272ca632f6c101f231"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c56" continuedAt="Text_95c976a2eec04e9289aa18116e6515c57">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f231" continuedAt="Text_28567aedb1e54e849272ca632f6c101f232"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c57" continuedAt="Text_95c976a2eec04e9289aa18116e6515c58">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f232" continuedAt="Text_28567aedb1e54e849272ca632f6c101f233"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c58" continuedAt="Text_95c976a2eec04e9289aa18116e6515c59">
<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&#xA0;March 31, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f233" continuedAt="Text_28567aedb1e54e849272ca632f6c101f234"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c59" continuedAt="Text_95c976a2eec04e9289aa18116e6515c510">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f234" continuedAt="Text_28567aedb1e54e849272ca632f6c101f235"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c510" continuedAt="Text_95c976a2eec04e9289aa18116e6515c511">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e04081c13bbe48d3bb9b3d0cca81d860" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_eccc4161cecb4e0e9bd2f79ccde27795" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction></ix:nonFraction> percent convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2d011315162b43398edc4d43f61dfe90" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_040223863f694143aeafc77acbcabb62" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction></ix:nonFraction>% Notes;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f235" continuedAt="Text_28567aedb1e54e849272ca632f6c101f236"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c511" continuedAt="Text_95c976a2eec04e9289aa18116e6515c512">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_00ed48c13a3e41a59f57e78e32a2e336" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5765a5913d9b40179d92f2285226cd54" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction></ix:nonFraction>% Notes;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f236" continuedAt="Text_28567aedb1e54e849272ca632f6c101f237"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c512" continuedAt="Text_95c976a2eec04e9289aa18116e6515c513">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f237" continuedAt="Text_28567aedb1e54e849272ca632f6c101f238"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c513" continuedAt="Text_95c976a2eec04e9289aa18116e6515c514">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f238" continuedAt="Text_28567aedb1e54e849272ca632f6c101f239"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c514" continuedAt="Text_95c976a2eec04e9289aa18116e6515c515">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f239" continuedAt="Text_28567aedb1e54e849272ca632f6c101f240"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c515" continuedAt="Text_95c976a2eec04e9289aa18116e6515c516">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">16</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f240" continuedAt="Text_28567aedb1e54e849272ca632f6c101f241"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c516" continuedAt="Text_95c976a2eec04e9289aa18116e6515c517">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f241" continuedAt="Text_28567aedb1e54e849272ca632f6c101f242"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c517" continuedAt="Text_95c976a2eec04e9289aa18116e6515c518">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three months ended&#xA0;March 31, 2021, common stock from our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ee8886a9310f4ddcb2b7947762657218" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> percent convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_792fe9322e4d409886378b2e066f65f0" contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes, would also have had an anti-dilutive effect on net loss per share.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f242" continuedAt="Text_28567aedb1e54e849272ca632f6c101f243"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c518" continuedAt="Text_95c976a2eec04e9289aa18116e6515c519">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f243" continuedAt="Text_28567aedb1e54e849272ca632f6c101f244"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c519" continuedAt="Text_95c976a2eec04e9289aa18116e6515c520">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three months ended&#xA0;March 31, 2022, common stock from the following would also have had an anti-dilutive effect on net loss per share:</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f244" continuedAt="Text_28567aedb1e54e849272ca632f6c101f245"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c520" continuedAt="Text_95c976a2eec04e9289aa18116e6515c521">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f245" continuedAt="Text_28567aedb1e54e849272ca632f6c101f246"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c521" continuedAt="Text_95c976a2eec04e9289aa18116e6515c522">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_acf69492fc724c92b962b1e11e2eaa4d" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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_0a206797b8c743759065e28eac72a546" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes; and</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f246" continuedAt="Text_28567aedb1e54e849272ca632f6c101f247"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c522" continuedAt="Text_95c976a2eec04e9289aa18116e6515c523">
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f1a39fa9afdb444ca040fa8fd4e57b4a" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes.</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f247" continuedAt="Text_28567aedb1e54e849272ca632f6c101f248"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c523" continuedAt="Text_95c976a2eec04e9289aa18116e6515c524">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f248" continuedAt="Text_28567aedb1e54e849272ca632f6c101f249"><ix:continuation id="Text_95c976a2eec04e9289aa18116e6515c524">
<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, 2022, we had warrants related to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2ad3f2367557405a8c6d2324e912a59a" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_abddc1cdda9749a6b8af5dd8ac5eb3c8" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f249" continuedAt="Text_28567aedb1e54e849272ca632f6c101f250">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f250" continuedAt="Text_28567aedb1e54e849272ca632f6c101f251"><ix:nonNumeric name="us-gaap:DebtPolicyTextBlock" id="Text_6c532e56086147ee8142945e5d038e81" contextRef="c20220101to20220331" escape="true" continuedAt="Text_2c7d2a10874c49ea8ed6194c9a7c56081">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f251" continuedAt="Text_28567aedb1e54e849272ca632f6c101f252"><ix:continuation id="Text_2c7d2a10874c49ea8ed6194c9a7c56081" continuedAt="Text_2c7d2a10874c49ea8ed6194c9a7c56082">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f252" continuedAt="Text_28567aedb1e54e849272ca632f6c101f253"><ix:continuation id="Text_2c7d2a10874c49ea8ed6194c9a7c56082">
<div 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 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. We record the entire debt issuance costs as a contra-liability on our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fa35c62ae15545fda47bd92f0ec9050d" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dfae12bf8c0d4b1fa86a0ad27d83e519" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4104add5953b45b09004aee6e573d81f" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_23f33708bb144c8896edb768bcc0da12" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes over the respective contractual term using an effective interest rate of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_1f8672f0057c4cd3ba9ee1a3d610959e" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_63df7b45bec94d108f6f2369726dcb1c" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.5</ix:nonFraction></ix:nonFraction> percent for each note. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible Debt</span>, for further details on our convertible debt instruments.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f253" continuedAt="Text_28567aedb1e54e849272ca632f6c101f254">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f254" continuedAt="Text_28567aedb1e54e849272ca632f6c101f255"><ix:nonNumeric name="us-gaap:DerivativesPolicyTextBlock" id="Text_2e3f06f0c3b242259c5e79489eed6c80" contextRef="c20220101to20220331" escape="true" continuedAt="Text_37742cfc44c148e694667f7584dc825f1">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f255" continuedAt="Text_28567aedb1e54e849272ca632f6c101f256"><ix:continuation id="Text_37742cfc44c148e694667f7584dc825f1" continuedAt="Text_37742cfc44c148e694667f7584dc825f2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f256" continuedAt="Text_28567aedb1e54e849272ca632f6c101f257"><ix:continuation id="Text_37742cfc44c148e694667f7584dc825f2">
<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 <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2de199144db84606922afa28c32d16ec" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f0716a76728945aeacfc77c73b2d1ec7" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f257" continuedAt="Text_28567aedb1e54e849272ca632f6c101f258">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f258" continuedAt="Text_28567aedb1e54e849272ca632f6c101f259"><ix:nonNumeric name="us-gaap:SegmentReportingPolicyPolicyTextBlock" id="Text_a592a963d50b4e51a05a26c3eb689d06" contextRef="c20220101to20220331" escape="true" continuedAt="Text_e79269c634824306ac07d2397e7c559b1">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f259" continuedAt="Text_28567aedb1e54e849272ca632f6c101f260"><ix:continuation id="Text_e79269c634824306ac07d2397e7c559b1" continuedAt="Text_e79269c634824306ac07d2397e7c559b2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f260" continuedAt="Text_28567aedb1e54e849272ca632f6c101f261"><ix:continuation id="Text_e79269c634824306ac07d2397e7c559b2">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e">single</span> segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f261" continuedAt="Text_28567aedb1e54e849272ca632f6c101f262">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f262" continuedAt="Text_28567aedb1e54e849272ca632f6c101f263"><ix:nonNumeric name="us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy" id="Text_fabff55575924204ab4d0d1a53d5fb8f" contextRef="c20220101to20220331" escape="true" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f971">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f263" continuedAt="Text_28567aedb1e54e849272ca632f6c101f264"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f971" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f972">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f264" continuedAt="Text_28567aedb1e54e849272ca632f6c101f265"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f972" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f973">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our 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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f265" continuedAt="Text_28567aedb1e54e849272ca632f6c101f266"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f973" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f974">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f266" continuedAt="Text_28567aedb1e54e849272ca632f6c101f267"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f974" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f975">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f267" continuedAt="Text_28567aedb1e54e849272ca632f6c101f268"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f975" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f976">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f268" continuedAt="Text_28567aedb1e54e849272ca632f6c101f269"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f976" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f977">
<div 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>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">17</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f269" continuedAt="Text_28567aedb1e54e849272ca632f6c101f270"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f977" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f978">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f270" continuedAt="Text_28567aedb1e54e849272ca632f6c101f271"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f978" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f979">
<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.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f271" continuedAt="Text_28567aedb1e54e849272ca632f6c101f272"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f979" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9710">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f272" continuedAt="Text_28567aedb1e54e849272ca632f6c101f273"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9710" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9711">
<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&#xA0;March 31, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f273" continuedAt="Text_28567aedb1e54e849272ca632f6c101f274"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9711" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9712">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f274" continuedAt="Text_28567aedb1e54e849272ca632f6c101f275"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9712" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9713"><ix:nonNumeric name="us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" id="Text_bd2546acd7db40c8a7bd10022a59ff6d" contextRef="c20220101to20220331" escape="true" continuedAt="Text_d647a5a2c2874eccb83a5d35dd2fb38f1">
<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>
</ix:nonNumeric></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f275" continuedAt="Text_28567aedb1e54e849272ca632f6c101f276"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9713" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9714"><ix:continuation id="Text_d647a5a2c2874eccb83a5d35dd2fb38f1" continuedAt="Text_d647a5a2c2874eccb83a5d35dd2fb38f2">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">Risk-free interest rate</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_ffb253cdaa2c497d9f158f41530bd3b8" contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">1.7</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_e90f6a95b57e4e9785b5740f296f22cb" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.5</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_7dae66b76386466dbd8280f7df578286" contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" 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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_6fd1d504e21a42f18d1513595b6d94a7" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </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;">Volatility</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_6c30560991c34955ac78828b469d91f7" contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">55.2</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_470fb7c2bc154d46b527889f6bc045b5" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">55.1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life*</div></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: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_e3f0b01c2b014194af0169f71cb6cace" contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" format="ixt-sec:duryear">6.3</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_c25f6066e793481b89742397fce1babb" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" format="ixt-sec:duryear">4.9</ix:nonNumeric> years</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f276" continuedAt="Text_28567aedb1e54e849272ca632f6c101f277"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9714" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9715"><ix:continuation id="Text_d647a5a2c2874eccb83a5d35dd2fb38f2" continuedAt="Text_d647a5a2c2874eccb83a5d35dd2fb38f3">
<div><br /></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f277" continuedAt="Text_28567aedb1e54e849272ca632f6c101f278"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9715" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9716"><ix:continuation id="Text_d647a5a2c2874eccb83a5d35dd2fb38f3">
<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">
  <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;"><ix:footnote id="Foot_74bbbb57209c4f53960b9d7c3438ee6b" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_b2ac901653d54e2fadb1e34420e76d70" contextRef="c20220101to20220331_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_658bc4cd50024cbc9d7a903e428fbe7f" contextRef="c20220101to20220331_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" format="ixt-sec:durwordsen">ten years</ix:nonNumeric> for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the three months ended March 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f278" continuedAt="Text_28567aedb1e54e849272ca632f6c101f279"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9716" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9717">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f279" continuedAt="Text_28567aedb1e54e849272ca632f6c101f280"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9717" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9718"><ix:nonNumeric name="us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" id="Text_ed6872a6ffbb45b4b4afd44a763ec080" contextRef="c20220101to20220331" escape="true" continuedAt="Text_c9b795bd5f974cea9de885312cf246a51">
<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>
</ix:nonNumeric></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f280" continuedAt="Text_28567aedb1e54e849272ca632f6c101f281"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9718" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9719"><ix:continuation id="Text_c9b795bd5f974cea9de885312cf246a51">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">Risk-free interest rate</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_77dd56e1caba4fc6aea5e9e6e638ae5c" contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_4d0a456ae4dc4871b24fbb25908cd45b" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_6ca23795eddd40b2a9ffe6e5b60ab59e" contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" valign="bottom" 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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_c44f5d5a2f164df58a55c39c846c87a6" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </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;">Volatility</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_bd9236668f60473db27e250b8060dc0d" contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">50.2</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_b5d4da261dad4007b283535f0efbd4b2" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">39.1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div></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: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_4cc29778c0e447968d90cd4b1be3691e" contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_6e6a732476bd479cad0b8af2fbcf4659" contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f281" continuedAt="Text_28567aedb1e54e849272ca632f6c101f282"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9719" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9720">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f282" continuedAt="Text_28567aedb1e54e849272ca632f6c101f283"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9720" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9721">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f283" continuedAt="Text_28567aedb1e54e849272ca632f6c101f284"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9721" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9722">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f284" continuedAt="Text_28567aedb1e54e849272ca632f6c101f285"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9722" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9723">
<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 <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_27893998ace24d7cb0e5fa8a728fcf92" contextRef="c20220101to20220331_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="c20220101to20220331_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="c20220101to20220331_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, 2022 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_7654fd0b1d374d55b0c76914d3cd1ad7" contextRef="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">33.08</ix:nonFraction> per share.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f285" continuedAt="Text_28567aedb1e54e849272ca632f6c101f286"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9723" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9724">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f286" continuedAt="Text_28567aedb1e54e849272ca632f6c101f287"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9724" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9725">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f287" continuedAt="Text_28567aedb1e54e849272ca632f6c101f288"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9725" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9726">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f288" continuedAt="Text_28567aedb1e54e849272ca632f6c101f289"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9726" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9727">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other executive officers. 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="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U013" 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="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" 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="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" 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="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_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="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_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>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">18</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f289" continuedAt="Text_28567aedb1e54e849272ca632f6c101f290"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9727" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9728">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f290" continuedAt="Text_28567aedb1e54e849272ca632f6c101f291"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9728" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9729">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our executive officers for the three months ended&#xA0;March 31, 2022 and 2021 were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_f686380f406d44659451af43ea4a98c6" contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">42.28</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_f37b71af46f844b7971b1a2b89993315" contextRef="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">77.17</ix:nonFraction> per share, respectively.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f291" continuedAt="Text_28567aedb1e54e849272ca632f6c101f292"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9729" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9730">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f292" continuedAt="Text_28567aedb1e54e849272ca632f6c101f293"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9730" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9731"><ix:nonNumeric name="us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" id="Text_e92c56e869754c4ead60123e84fe8e44" contextRef="c20220101to20220331" escape="true" continuedAt="Text_6830ba26127a4b9ab2d08f477aa9b8381">
<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&#xA0;March 31, 2022 and 2021 (in thousands).</div>
</ix:nonNumeric></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f293" continuedAt="Text_28567aedb1e54e849272ca632f6c101f294"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9731" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9732"><ix:continuation id="Text_6830ba26127a4b9ab2d08f477aa9b8381" continuedAt="Text_6830ba26127a4b9ab2d08f477aa9b8382">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f294" continuedAt="Text_28567aedb1e54e849272ca632f6c101f295"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9732" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9733"><ix:continuation id="Text_6830ba26127a4b9ab2d08f477aa9b8382">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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</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:AllocatedShareBasedCompensationExpense" id="Fact_99e0a32e2d2345afb5dae8769531813a" contextRef="c20220101to20220331_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">160</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:AllocatedShareBasedCompensationExpense" id="Fact_40be1fccef3b4d09a3e3fd20a32e9617" contextRef="c20210101to20210331_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent 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:AllocatedShareBasedCompensationExpense" id="Fact_d17f71a28c014450810cc3b1536b5b8b" contextRef="c20220101to20220331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">19,082</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:AllocatedShareBasedCompensationExpense" id="Fact_3c2e5d8e247446ac9584c5c2161ac0d5" contextRef="c20210101to20210331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">25,899</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%; 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="c20220101to20220331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,994</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="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>
  </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</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:AllocatedShareBasedCompensationExpense" id="Fact_86792c009d4e41b3a08f1d4f8e56e11b" contextRef="c20220101to20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">26,236</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="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>
  </tr>
</table>
</ix:continuation></ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f295" continuedAt="Text_28567aedb1e54e849272ca632f6c101f296"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9733" continuedAt="Text_90cf21f3c5fc4b258bae8f53bb046f9734">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f296" continuedAt="Text_28567aedb1e54e849272ca632f6c101f297"><ix:continuation id="Text_90cf21f3c5fc4b258bae8f53bb046f9734">
<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, 2022, 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="c20220331_AwardTypeAxis_EmployeeStockOptionMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">67.7</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_221a3013ba19446cad9c335f9391fa1a" contextRef="c20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">69.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_1a5a87c9d0c04b5799a90b3d2965c63f" contextRef="c20220331_AwardTypeAxis_PerformanceSharesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">5.4</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_13a68deb2d8d496a9b99b31f4abcfe12" contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember" format="ixt-sec:duryear">1.4</ix:nonNumeric> years, <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_94356ff2a4564b669110ba6365630dc9" contextRef="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember" format="ixt-sec:duryear">1.7</ix:nonNumeric> years and <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_715166969b8f40d5bb56857e5eca4ce6" contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:duryear">1.6</ix:nonNumeric> years, respectively.</div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f297" continuedAt="Text_28567aedb1e54e849272ca632f6c101f298">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f298" continuedAt="Text_28567aedb1e54e849272ca632f6c101f299"><ix:nonNumeric name="us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock" id="Text_8374d619cf954b9fa63d83447841042a" contextRef="c20220101to20220331" escape="true" continuedAt="Text_65e610b11ba7489a85e0d35a363e75f11">
<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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f299" continuedAt="Text_28567aedb1e54e849272ca632f6c101f300"><ix:continuation id="Text_65e610b11ba7489a85e0d35a363e75f11" continuedAt="Text_65e610b11ba7489a85e0d35a363e75f12">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_28567aedb1e54e849272ca632f6c101f300"><ix:continuation id="Text_65e610b11ba7489a85e0d35a363e75f12">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any recently issued accounting standards to have a material impact to our financial results.</div>
</ix:continuation></ix:continuation></div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:InvestmentTextBlock" id="Text_b6e1a67fcacc41d1be3b24f234df60ad" contextRef="c20220101to20220331" escape="true" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac81">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3.&#160; Investments</div>
</ix:nonNumeric><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac81" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac82">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac82" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac83"><ix:nonNumeric name="us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock" id="Text_88180c6e643a4b7eb3d2e8e8e7abb05a" contextRef="c20220101to20220331" escape="true" continuedAt="Text_f3c8ffbcae054b50963bff74372334f61">
<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, 2022:</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac83" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac84"><ix:continuation id="Text_f3c8ffbcae054b50963bff74372334f61" continuedAt="Text_f3c8ffbcae054b50963bff74372334f62">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac84" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac85"><ix:continuation id="Text_f3c8ffbcae054b50963bff74372334f62">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; 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;"><span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_4b3282e6abbf4694b90d56a12cb3a78d" contextRef="c20220101to20220331" format="ixt-sec:durwordsen">One year</ix:nonNumeric></span> or less</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" id="Fact_26a36804df4340729bec0b2f463acda4" contextRef="c20220331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">63</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%;"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_3bd993e525784a5398b297b7856fe228" contextRef="c20220101to20220331" format="ixt-sec:durwordsen">one year</ix:nonNumeric></span> but within <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3" contextRef="c20220101to20220331" format="ixt-sec:durwordsen">two years</ix:nonNumeric></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%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="Fact_b3c2ee50dd694d208197df43360458a9" contextRef="c20220331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">30</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 <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_812c571149d64b329fe4410606d76c7a" contextRef="c20220101to20220331" format="ixt-sec:durwordsen">two years</ix:nonNumeric></span> but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797">three and a half years</span></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="c20220331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">7</ix:nonFraction></div></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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px;"><div style="text-align: left; 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="c20220331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac85" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac86">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac86" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac87">
<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, 2022, <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_ecfa1cb8a4484b48a192e8436b1431fe" contextRef="c20220331" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">93</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_34c87d75876e42c988ffebc06f56b6a3" contextRef="c20220101to20220331" format="ixt-sec:durwordsen">two years</ix:nonNumeric>.</div>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac87" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac88">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac88" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac89">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.</div>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac89" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac810">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac810" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac811">
<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>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac811" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac812">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac812" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac813">
<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, 2022, we had an ownership interest of less than 20 percent in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b7edbc55e46842cb916a4ced56279788" contextRef="c20220331" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction> private companies and <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8144a98eb4174391a5f3065f3f804da4" contextRef="c20220331" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</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, YourBio Health, Inc. and Suzhou-Ribo Life Science Co, Ltd. The publicly traded companies are Antisense Therapeutics Ltd., Bicycle and ProQR.</div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">19</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac813" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac814">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac814" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac815"><ix:nonNumeric name="us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock" id="Text_b7c74c13c32e406597a8b0ef49047c5a" contextRef="c20220101to20220331" escape="true" continuedAt="Text_1509de82635045edb6304b603e82718a1">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac815" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac816"><ix:continuation id="Text_1509de82635045edb6304b603e82718a1" continuedAt="Text_1509de82635045edb6304b603e82718a2">
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac816" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac817"><ix:continuation id="Text_1509de82635045edb6304b603e82718a2" continuedAt="Text_1509de82635045edb6304b603e82718a3">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td 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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;">Amortized</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</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; border-bottom: #000000 solid 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">March 31, 2022</span></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;">Cost</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;">Gains</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;">Losses</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Available-for-sale securities:</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_7842515e18104a5cafcff84ddb01d951" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">420,081</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_c7e1b54bc6f94cda93f41712a4a9675c" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">131</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_6987932b0c734a95908cba3dde93f730" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,766</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_35d357c29e5b420daf82588703d78d8d" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">418,446</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_80e0d5c6be1c4870adc06685000bf257" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,407</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_18ba7ad7166c418da8278eb1c1894a6f" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_e9cc451da55c4d1c9aa3ad82c7ca9aae" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">49</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_9e8a5c54173d453cb9fb728033354336" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,358</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 (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#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="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">330,358</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="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,133</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_cf007fb70961423eb9a3dd191872008b" contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">329,226</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_7c05793868aa4afb94fcfb88fcffcb2b" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">158,548</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="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#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_3e3856bd21754e01ab011686088d0aa5" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">376</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_893fcba0e0004d12b5940266add3822a" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">158,173</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_119b425fc08349cfbe3d5f2787dfca82" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,419</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="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" 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_e14c8b798e654a2ab567476189066f11" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">99</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_48196ae3d4df4f8195e5c9e5179b69ee" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,320</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_3e165eb36915445a94e7bca3626be047" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">949,813</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_3c026731cf6c4d2c9f3bb6487eb52874" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">133</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_cbaf34a8cf1344ed8d1c9bd3764052c6" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,423</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_401ef7ec0ee84b33b734c6646f73945d" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">946,523</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_e739ce406a594fdab205b3f709378b35" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">345,813</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="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">24</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="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">10,275</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="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">335,562</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="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">72,844</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="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_8c034ba7ebd94e519637bf63e04e1b9f" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,974</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="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">70,870</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="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">164,040</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="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">70</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="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,544</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="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">161,566</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;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#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_9945c8a3aa274e52aa7dfeabc6567ab4" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,995</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_2aa6d352ef954e92b94b3e1d7fb0194a" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_e6854048f6c941b08d43417760c49b8d" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">818</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_d4953054b98b42dba9d5bed9a4393226" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">34,177</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 securities with a maturity of more than one year</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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_2b2ee63d727e423482b317c18a37ce81" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">617,692</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_22456af2bd1a42a5aaa84149b3a6373e" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">94</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_3f93907b739e4f8a80f71070bbbc98e2" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,611</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_33930b14001f46ccb9bf26b44f06a253" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">602,175</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: 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;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: '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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_c63efe923e13426992c34154ca0ceb66" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,567,505</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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_4d9475d7048b443985ccf0e54c482dde" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">227</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_abe680e773e045d898d7e780327a8001" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">19,034</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;"><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;"><div style="font-family: '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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ed64a9779a3842959199d38607dc68f6" contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,548,698</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;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div></td>
    <td colspan="1" 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:EquitySecuritiesFvNiCost" id="Fact_795298199a7149089987fd608d910788" contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,897</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedGain" id="Fact_95a1e63d6d4c49f48092f55cc7344a6f" contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,946</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <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:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_720e14f204184668ac412128829c1d4c" contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,274</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%;"><div style="font-family: '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:EquitySecuritiesFvNi" id="Fact_c9668cdfca24444facba84f5586a8b21" contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,569</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;">Total equity securities included in deposits and other assets (3)</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_642c9681829a411280b706605512aec4" contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">23,115</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_5465f26f407f4c8cbf1a7f4bc78d58bb" contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16,707</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_8f26e7f4482346919fb9fd971a0e1bd2" contextRef="c20220101to20220331_FinancialInstrumentAxis_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; 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_c86ece7c238c409db75f4e86d57eaa03" contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">39,822</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 equity securities</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_74700e6175be499286aad7c1da529560" contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">35,012</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_023010caa8f343509b0246de63732628" contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">20,653</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_b4350186c9724e47b1cac8c01c4216b9" contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,274</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:EquitySecuritiesFvNi" id="Fact_10dc545d20404abda7146b5a706c0e00" contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">51,391</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: 4px; 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 and equity securities</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:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_6c45e37635ae4e82a8fe9a524ce7bc4f" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,602,517</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_5ab4e59a3fb946b2bfa63a42fd6cc9c5" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">20,880</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_571cea17cf8743fbb59b7749cbf08cd2" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">23,308</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>
    <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:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_29d056dd0bc546a5b95f13a73db1588f" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,600,089</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac817" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac818"><ix:continuation id="Text_1509de82635045edb6304b603e82718a3" continuedAt="Text_1509de82635045edb6304b603e82718a4">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac818" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac819"><ix:continuation id="Text_1509de82635045edb6304b603e82718a4" continuedAt="Text_1509de82635045edb6304b603e82718a5">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td 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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;">Amortized</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</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;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</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; border-bottom: #000000 solid 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">December 31, 2021</span></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;">Cost</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;">Gains</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;">Losses</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Available-for-sale securities:</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_b358568c049541b1856e64106205b629" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">383,870</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_870aab605dd4403c879855738490612a" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">728</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">226</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_baf860337cb14231b2612b277c5a61c8" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">384,372</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_68fdb285d5a54bedba4551932330f29f" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">48,493</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_90dbffe642224d96bbf19226414d77d9" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">19</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_1777d6b10a6444f78df8d692409a590a" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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_2130cf6d51914dc0afd1eccb0e4dfdad" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">48,494</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 (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#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_d8fc413c165c4a2c8aa4472257c08e29" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">45,424</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_c7bb5d4884cd42d0a8a8ff87cdcd691a" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_32a3a41f82bb44c799d99e85af07437d" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">64</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_4ed162913c2d4a49b2bae214aa82a90e" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">45,360</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;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#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_e6152f86899e46e196de685960cf0520" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">134,770</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_976e0d2fac214a4a8ce8d68be3812eda" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">45</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_e332742abab244fa8bc1de590d821dcc" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">37</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_072984a5e1e94320b84fd889d20ca860" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">134,778</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 securities with a maturity of one year or less</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_5d62eb1de663460d8a9d559d81878a58" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">612,557</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_32d0c20dd09a4965be6545f5ef1e1d0e" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">792</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_a65f661f76de418c8ded0d80f7684b50" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">345</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_5269f1e3ba9b4b5f9397e201edccca32" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">613,004</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;">Corporate debt securities</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_a2fd30f9900b415194cd94d357af784b" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">382,000</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_34ab02ad304f441abe8a81962651c7ce" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">331</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_3d4b4abb3a29485786b07cbc63b828cb" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,644</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_e00dab3b4cb04062a2e6a17f853d0e52" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">379,687</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 U.S. government agencies</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" 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_d714f0d4eecc4d92b9b830449bba7fd1" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">72,935</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_270ced43418a4c2faa9a7f0a3bd756eb" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_cc8c6fd4825a4a8ca13fdce32ea0a599" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">561</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_11b446490081470aa73bc2871b0b1042" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">72,374</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 the U.S. Treasury</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_e8d68ba6fad84cecafc9cdd32dea1e2f" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">137,635</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_28fa2a9aa6c3425bb5c7af4315f2d4c3" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">139</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_feb5ebb376f64b648a49adafb20944f7" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">500</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_5a7c49cad6044951b9d764adb62179ca" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">137,274</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 states of the U.S. and political subdivisions of the states</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_b4ec0071c45247e3b27a4b280e593780" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">39,909</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_31520233cfb642e0bb7685bb15133f3a" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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_81b005a6831247d6a900198d8738b3d0" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">224</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_e281a6848521414491c86fcd9f85c8a9" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">39,686</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;">Other municipal debt securities</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_8039b5caa1e74523933ab777edc0cc55" contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,136</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_ce80a712118d48bca2b5173f22d877be" contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" 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:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_7f14ae8a216045b6b0f1cba03a06d496" contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">37</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_5191d04da6c34987a3faa2edb62ca0eb" contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,099</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 securities with a maturity of more than one year</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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_d8f9bd55d10c46e8a7923b828bf66f7b" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">638,615</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_9edb30f88d124e4f98e5fc6733baa317" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">471</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_35b1772ea2884933bfa48eab5441097a" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,966</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_bd78e79378ff4eecb24ada86ee7d4685" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">635,120</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: 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;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: '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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_d8842e093daf4aa8a441e191da86ea99" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,251,172</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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_4a16a27e0c4144fea9d33948c111d40b" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,263</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_5d60bf6074c241728013af9aebe4f553" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,311</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;"><div style="font-family: '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;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_282a1da5440143508a579978a45d2601" contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,248,124</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;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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: 52%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div></td>
    <td colspan="1" 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:EquitySecuritiesFvNiCost" id="Fact_b8a712e5f4af42cdb9018ff5937f5e79" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,897</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedGain" id="Fact_8b35758c336d4c378e03fdeaeaa046d7" contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">7,145</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <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:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_d23a46f787e04e259237398f99054fea" contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">837</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%;"><div style="font-family: '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:EquitySecuritiesFvNi" id="Fact_8651c4c7cf0b40ec9603b79cfd50d43b" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,205</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;">Total equity securities included in deposits and other assets (3)</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_2faff3973c0f4ab0bd4fcffd3307bce8" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">15,615</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_e3dee8ea479d4e8fbda5e68ba7814a7e" contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16,707</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_53a829bbd230481e83c9e355f575a8b7" contextRef="c20210101to20211231_FinancialInstrumentAxis_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; 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_90b3f028c4c64df180eb902de39038aa" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">32,322</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 equity securities</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_cfbea931b88e4baf9112a7e54d02cbfc" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">27,512</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_5e7e8a83411f4b40bf00d16a3e60d487" contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">23,852</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_d45ad7a12cac403ea2d5a2edb37a0eed" contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">837</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:EquitySecuritiesFvNi" id="Fact_8bd47c89fd1645cfa78adda562a9364e" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">50,527</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: 4px; 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 and equity securities</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:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_6808aa03681547cca1d6c98d32aab031" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,278,684</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_f7a5c21d883b40c784a842b4eab86b9d" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">25,115</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_bf106be9d5824af3aa9e4c635557fb8a" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,148</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>
    <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:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_ecad1868d9ae4c4cb68ebd3c78a85d30" contextRef="c20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,298,651</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac819" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac820"><ix:continuation id="Text_1509de82635045edb6304b603e82718a5" continuedAt="Text_1509de82635045edb6304b603e82718a6">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac820" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac821"><ix:continuation id="Text_1509de82635045edb6304b603e82718a6" continuedAt="Text_1509de82635045edb6304b603e82718a7">
<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">
  <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;"><ix:footnote id="Foot_2ec4116852e041e3a2a38cb16ff4ea22" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac821" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac822"><ix:continuation id="Text_1509de82635045edb6304b603e82718a7" continuedAt="Text_1509de82635045edb6304b603e82718a8">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac822" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac823"><ix:continuation id="Text_1509de82635045edb6304b603e82718a8" continuedAt="Text_1509de82635045edb6304b603e82718a9">
<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">
  <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;"><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 <ix:nonFraction name="ions:NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" id="Fact_602d828e78234435b39c13dda2bf144d" contextRef="c20220331" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> publicly traded companies, ProQR and Bicycle, which we classify as Level 1 and Level 3 investments, respectively. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2022, we recognized a $<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_8c163df244e8495f8c0396f6ec856bf4" contextRef="c20220101to20220331_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">3.4</ix:nonFraction> million and a $<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_cec1b18fe8e84d1ba09baf2edef0616b" contextRef="c20220101to20220331_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">3.2</ix:nonFraction> million unrealized loss on our condensed consolidated statement of operations related to our investments in ProQR and Bicycle, respectively. In the three months ended March 31, 2021, our equity securities included in other current assets only consisted of ProQR.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac823" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac824"><ix:continuation id="Text_1509de82635045edb6304b603e82718a9" continuedAt="Text_1509de82635045edb6304b603e82718a10">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac824" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac825"><ix:continuation id="Text_1509de82635045edb6304b603e82718a10">
<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">
  <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;"><ix:footnote id="Foot_55aad856d839435daad2d772a2ea1bc5" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus 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></ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">20</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac825" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac826">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac826" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac827"><ix:nonNumeric name="us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" id="Text_f990914388cd4584984855ae82ba9a6b" contextRef="c20220101to20220331" escape="true" continuedAt="Text_87351a179bbc49b1aa23a67bd9c7c0cf1">
<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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands, except for number of investments). 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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac827" continuedAt="Text_67c5134ce19f494e9c39151ecf9c3ac828"><ix:continuation id="Text_87351a179bbc49b1aa23a67bd9c7c0cf1" continuedAt="Text_87351a179bbc49b1aa23a67bd9c7c0cf2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_67c5134ce19f494e9c39151ecf9c3ac828"><ix:continuation id="Text_87351a179bbc49b1aa23a67bd9c7c0cf2">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="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;">Less than 12 Months of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="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;">More than 12 Months of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="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;">Total Temporary</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div></td>
    <td colspan="1" 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; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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" 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: 16%; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_333cdd7221c74a659058428cb96f027e" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U011" decimals="0" scale="0" format="ixt:numdotdecimal">337</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_2e0cac4f3e6445e4af1d421cd8ba2264" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">647,390</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_903a58d3bf3c421b9166ac1d0a37f22d" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,694</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_183b7171ce6948fe93c1afb5708dc040" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,300</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_2bc4f2d4d6bd455e9474ce6348458023" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">347</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_39ca68f5ced34e02a3fb7f209ed77346" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">658,690</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_6a521c4aea4b4d6186a40cc4ac11ef16" contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">12,041</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 16%; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_f82ef35b85bc4b76a2ca3ea408acca74" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U011" decimals="0" scale="0" format="ixt:numdotdecimal">14</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_0a9f0760b76943a0bb457df5aa11d275" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">95,543</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_a606df5dbef24526ade176d96aa0c07b" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,697</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%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_2d0505e6d78b437083a13a36af9d0e35" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">9,685</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_be6630f1d422413eb69c31e0abbb4c84" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" 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%; 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%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_9e4b0d43d3f14d11b3cdc492ef07dd02" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">105,228</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_eba3f72c498e466687adcba61f086b48" contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">2,023</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: 16%; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_2e46b5062fb3478c908336d6d2d994c6" contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U011" decimals="0" scale="0" format="ixt:numdotdecimal">44</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_392a47ad8b314b019fde0f086884f91a" contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">406,747</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_b473b5a2bf6f472895d5dbf195a86994" contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,539</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; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_631f14e2221f4205b5b6af1f14754c3c" contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">4,860</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_366adc85dd3e4261abd0ad4c81e9ed06" contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">138</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; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_8fe8a8c8d9ba4dbe9a0815a2dd6c7215" contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">411,607</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_039c758638b24f77831d5dfe6f4ab76e" contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,677</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 16%; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_2cef1dcb51a449edb7fe76af4b2c0e0c" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U011" decimals="0" scale="0" format="ixt:numdotdecimal">619</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_2b2f7503adc14be999f6518218accc8a" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">173,537</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_f999f2e853164a178503a3147b33ac68" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,096</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%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_1ee53f584ab24cb6b581f7eae1eba196" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,455</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_98453b0c0b144bba86ec994206fdc1cb" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">98</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%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_4d01726992bb4d94b31e50877ad828f0" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">178,992</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_401d55f983434e8d9399ad8c2fc7758d" contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,194</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: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_a21f49784eae40489b0406c92c97e44e" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U011" decimals="0" scale="0" format="ixt:numdotdecimal">3</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_ed6918e8de4a4cddb68b84b0973ef21c" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,315</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_eb8bb8a7eb794fd2aa573bebbef50d6c" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">16</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_fe22a62f0cae44359a1087d8ba07f963" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">5,005</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_e7162ed2803b4dcdb16f05d3cdc01bed" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">83</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_f5242826454a4306b595db9815050842" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,320</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_378bb0ac33e34dfdbe5d8fb3bf1f7047" contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">99</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: 16%; padding-bottom: 4px; white-space: nowrap;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
    <td 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;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_7e1f0b8e65b4437a89df6913266edd37" contextRef="c20220331" unitRef="U011" decimals="0" scale="0" format="ixt:numdotdecimal">1,017</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_a321ec73c6744478ab33de1911123ebf" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,324,532</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_32652639154d4153a0f3bf2d89e86160" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">18,042</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_c18b9c577f3c4038843a9b7ee496d0d4" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">36,305</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_b3760c7e65ef40e2ab47903dd7c9443a" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">992</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_08acbc6cc04049ed9b3d48be01027292" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,360,837</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_cf642061255f4432b68bd3618eb2a416" contextRef="c20220331" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">19,034</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>
  </tr>
</table>
</ix:continuation></ix:continuation></div>
<div style="text-align: left;"><br /></div>
<div><ix:nonNumeric name="us-gaap:FairValueDisclosuresTextBlock" id="Text_2a6de6f9bc2e421d838e9ff6c089fad5" contextRef="c20220101to20220331" escape="true" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4.&#160; Fair Value Measurements</div>
</ix:nonNumeric><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b1" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b2">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b2" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b3">
<div 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>
</ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b3" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b4">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b4" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b5"><ix:nonNumeric name="us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock" id="Text_3fc22c693e28451987436214b4939105" contextRef="c20220101to20220331" escape="true" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b1">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at March 31, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of March 31, 2022 and December 31, 2021, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our Bicycle investment was subject to trading restrictions that extend to the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.</span> The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b5" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b6"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b1" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b2">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b6" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b7"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b2" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b3">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td 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>
    <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, 2022</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;">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" 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;">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" 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;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
    <td colspan="1" 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: 52%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">407,399</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_435272b4ab6d4fb0a17848af08d9ea64" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">407,399</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:CashAndCashEquivalentsFairValueDisclosure" id="Fact_b9e898ee93984d899874de0b216f6350" contextRef="c20220331_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%; 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:CashAndCashEquivalentsFairValueDisclosure" id="Fact_ad9e4c4bff7e4a2395e4c4efbe25e180" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div></td>
    <td colspan="1" valign="bottom" 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_1b769ef466ea447fba9ad51918866940" contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">754,008</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_1a622d10285342d4ab574fbc330e9b6a" contextRef="c20220331_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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2a11d5be65ff43b2bc3316d459599b2f" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">754,008</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ff48b2cde78e4246b9f8c0d3668f45a9" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4ce9866198094ab9bb0fba527e9f7a46" contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">105,228</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_cc73c7dd4336416d8872098ddc72f3db" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" 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_418e9f44ebbb42dd9a510d3d5c448b72" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">105,228</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_63265628852a4ba29e93a651719977ed" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (4)</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_144b8361be90457089523a487891e260" contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">490,792</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_80cb88c905824e2f9a4af8d421a3ae6c" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">490,792</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2e48b747b93e49a19ff9c8c29a110e0c" contextRef="c20220331_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>
    <td colspan="1" valign="bottom" 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_a2102c4b8ddf44179d1593de5f225b5c" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (5)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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_c11eb07ea3324e24902d31be146e2aba" contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">192,350</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_5239338c06b14e6a85429a23967f6b00" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" 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_d3641150e44941fa942aa4dc4b80dcba" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">192,350</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><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4256bb9f94cb424da59655cd85ab7f9f" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></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><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" valign="bottom" 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_5a3e302889e04832960498aaf3fc8b2b" contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,320</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c79df577c73b4e58b8a6ebc687660780" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_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%; 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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0dfa9dad994240f3bfc133e3f1806e42" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,320</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><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_d9283a639225417ab2226e23faf78f90" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></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><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in Bicycle Therapeutics plc (6)</div></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:EquitySecuritiesFvNi" id="Fact_063ea3aa6c0446b1901c679162b7098d" contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,131</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:EquitySecuritiesFvNi" id="Fact_355b95f4be1a40aca92d8c591b590998" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember" 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:EquitySecuritiesFvNi" id="Fact_588d4799502645ff9bb47bcf9ef264fc" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember" 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><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_e2b3f77b6b2c4be3bafd76a92f2212c3" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,131</ix:nonFraction></div></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><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (6)</div></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:EquitySecuritiesFvNi" id="Fact_5715fb92aca2469f8d6b89bcc32dd2ad" contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">438</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_eaa3b06235c44c048a5d428f0fd68f15" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">438</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_816cd8cab6a1437db6b65fcb66362f2b" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember" 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_7130a91908584a7c9eff44721af2d068" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_9623b6fc811d446d8de6fe8c0a84d07a" contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,967,666</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_5e3adc88dc374a21be5199cc974a06ca" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">898,629</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_fb2ce086644c437499ac32ea8b2ab24d" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,057,906</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_7b5eb73a704b42f985034bdd93235dd2" contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">11,131</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b7" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b8"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b3" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b4">
<div><br /></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">21</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b8" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b9"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b4" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b5">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b9" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b10"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b5" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b6">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td 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>
    <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;">December 31, 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;">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" 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;">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" 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;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
    <td colspan="1" 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: 52%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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_3abef904d1ac4dac9365cd6a89ce306b" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">541,199</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_d7eb290d8c5b4341953ea8ce19b70167" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">541,199</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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:CashAndCashEquivalentsFairValueDisclosure" id="Fact_9d277c8fc4ff4a19a7ee29dcea9663b9" contextRef="c20211231_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%; 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:CashAndCashEquivalentsFairValueDisclosure" id="Fact_e0825e1067364ec09a168d5dbb04bd55" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</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_6d98cfd31fed4be1bc5dd4e5765ff970" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">764,059</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_880b4c0e0d2d48df987d8eb4b3893eda" contextRef="c20211231_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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_641d49c2d0c64af9adad977b14b03585" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">764,059</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0ccc9dc9ab324a0c8d69143093135087" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a02ee28d048e4f4a86d13e676be48142" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">120,868</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_2c0dd2ce365841a7940c2b161ab7aa5b" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" 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_276eb2ce23b74c76b7109fee3b729859" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">120,868</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_e9495bbff93745cdbd73aaf148a9dd4a" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%;"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (3)</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_92f2c745baa2467ebc8da9f308582732" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">182,634</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4f65ddc8bb1f41b18f4a4fafb05aa5bf" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">182,634</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_cad6d847f28b41d1ba345ee379c53c3a" contextRef="c20211231_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>
    <td colspan="1" valign="bottom" 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_a2deb395404a40e59f04a7af68529744" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_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: 52%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (7)</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_8ac6126992144e2d902abafe0f05aaf1" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">174,464</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_c4b11390dafb4d68ab357a12be102e2b" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" 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_984ae9d0003e4112b370b64ac08e73fa" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">174,464</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><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0602b31c9430474ba3e3239fa80848d7" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></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><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" valign="bottom" 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_3884240483e242908ec151549d8a9266" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,099</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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a95b8a716a024353bd232c9287cc39cc" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_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%; 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:AvailableForSaleSecuritiesDebtSecurities" id="Fact_bee8ae5848674561afc84c3a3eeddfb7" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">6,099</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><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_eda294b705b64b799f776b0e52f994d6" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:zerodash">&#8212;</ix:nonFraction></div></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><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in Bicycle Therapeutics plc (6)</div></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:EquitySecuritiesFvNi" id="Fact_18bb66a7c7c8455bbd8d594108704256" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,330</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:EquitySecuritiesFvNi" id="Fact_4a150c4659c644349b579e7a6f26e609" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember" 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:EquitySecuritiesFvNi" id="Fact_a3b9e5403eee4d9d87f1c1dfaf13ac3b" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember" 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><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_0f3b33ac1a704ec3b63b853cd5c2bef6" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,330</ix:nonFraction></div></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><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (6)</div></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:EquitySecuritiesFvNi" id="Fact_b0bdc20ef3184f16a0c2f40e12be4cfc" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,875</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_6a13d939e5dc429399070728b0932ea7" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">3,875</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_44d66cda97bb4fbc8cdd4b7bef54d977" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember" 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_236030e02f7644f8b79cdd10bd353619" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_d3bd323a8b614ca5970873ceac15876b" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,807,528</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_309c74f6dec14486a89fc6b78983b26a" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">727,708</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_11ff54c661534a3abddbec83ad68c19a" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">1,065,490</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_d6e03911cdb74cbaa033e42a7ae570af" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:numdotdecimal">14,330</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b10" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b11"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b6" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b7">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b11" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b12"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b7" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b8">
<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>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b12" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b13"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b8" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b9">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b13" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b14"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b9" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b10">
<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">
  <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;"><ix:footnote id="Foot_a07f61350d6c43dcbc95f9a5735b974a" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in cash and cash equivalents on our condensed consolidated balance sheet.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b14" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b15"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b10" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b11">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b15" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b16"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b11" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b12">
<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">
  <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;"><ix:footnote id="Foot_f8be77aa66f84482abc56f1b540c3aca" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f222017503d14900b7297dbf8ca32548" contextRef="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">13.5</ix:nonFraction> million was 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:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b16" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b17"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b12" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b13">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b17" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b18"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b13" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b14">
<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">
  <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;"><ix:footnote id="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in short-term investments.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b18" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b19"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b14" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b15">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b19" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b20"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b15" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b16">
<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">
  <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;"><ix:footnote id="Foot_f0cb78a83b31476988ccfd169edddb78" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_23950cfc108a4c58977c3255b2c7769a" contextRef="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">15.0</ix:nonFraction> million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.</ix:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b20" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b21"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b16" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b17">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b21" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b22"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b17" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b18">
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_2009e9e101cd4940acd892bb1ca9a15f" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_29824ec83f13463cb421396ade5c8f28" contextRef="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">10.3</ix:nonFraction> million was 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:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b22" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b23"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b18" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b19">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b23" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b24"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b19" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b20">
<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">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_4aceaee590d24617870bb41115adebfe" 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>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b24" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b25"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b20" continuedAt="Text_e419910cf55c4bcc8c7782fea0ab3f8b21">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b25" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b26"><ix:continuation id="Text_e419910cf55c4bcc8c7782fea0ab3f8b21">
<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">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_5b9b3c8599d14902835320847fbc6b63" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_08231978aefc42d3a9f2445f36d5a47c" contextRef="c20211231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">2.3</ix:nonFraction> million was 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:footnote></div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b26" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b27">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b27" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b28">
<div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Convertible Notes</div>
</ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b28" continuedAt="Text_8208e9fc30f64aa381857ab097cf449b29">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_8208e9fc30f64aa381857ab097cf449b29">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dfc304a4577d4a8b8ccf97e7be8f9791" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b605dc05faaa4ecf92f3388ccd8e6140" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>% Notes had a fair value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_886896b6a5b643a387fb328dcc366ca9" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">494.4</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_e2d5869342504cbea6cdb10162937afd" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">595.4</ix:nonFraction> million at March 31, 2022, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div>
</ix:continuation></div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:IncomeTaxDisclosureTextBlock" id="Text_5d168265bebe4eef9cbf660ffa2537c4" contextRef="c20220101to20220331" escape="true" continuedAt="Text_c4b1589a70184a6f9f453abd1e87aff71">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Income Taxes</div>
</ix:nonNumeric><ix:continuation id="Text_c4b1589a70184a6f9f453abd1e87aff71" continuedAt="Text_c4b1589a70184a6f9f453abd1e87aff72">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_c4b1589a70184a6f9f453abd1e87aff72">
<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 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over <ix:nonNumeric name="ions:AmortizationPeriodForResearchAndDevelopmentExpenditures" id="Fact_2705398e97944d39b41b282331559e11" contextRef="c20220101to20220331" format="ixt-sec:durwordsen">five years</ix:nonNumeric> pursuant to Internal Revenue Code, or IRC, Section 174. Although the U.S. Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified. As a result, we recorded a $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_1ddf6dc05f3447199bbd76650ac3a7b8" contextRef="c20220101to20220331" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">1.1</ix:nonFraction> million income tax expense for the three months ended&#xA0;March 31, 2022 compared to $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_d71da819015a406a9a7453adef2b9c98" contextRef="c20210101to20210331" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">0.1</ix:nonFraction> million income tax expense for the same period in 2021. </div>
</ix:continuation></div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">22</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:CollaborativeArrangementDisclosureTextBlock" id="Text_49a5ba0585764afaa86538e52aa60f04" contextRef="c20220101to20220331" escape="true" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6.&#160; Collaborative Arrangements and Licensing Agreements</div>
</ix:nonNumeric><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae1" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae2">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae2" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae3">
<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;">2022</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, 2021</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae3" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae4">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae4" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae5">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Strategic Partnership</div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae5" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae6">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae6" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae7">
<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>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae7" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae8">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae8" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae9">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, Angelman Syndrome, 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, 2022, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_4de0101278b94f98a15dfb2c4990f91e" contextRef="c20220331_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-8" scale="9" format="ixt:numdotdecimal">3.3</ix:nonFraction> billion from our Biogen collaborations.</div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae9" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae10">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae10" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae11"><ix:nonNumeric name="us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" id="Text_eb04b7475c5c4dcca50d4367953aaa84" contextRef="c20220101to20220331" escape="true" continuedAt="Text_dc5003216fc1445db606e7831e16f5221">
<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, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae11" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae12"><ix:continuation id="Text_dc5003216fc1445db606e7831e16f5221" continuedAt="Text_dc5003216fc1445db606e7831e16f5222">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae12" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae13"><ix:continuation id="Text_dc5003216fc1445db606e7831e16f5222">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties (commercial revenue)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3bfe46d312174a25a4dfa7f2fa45dd19" contextRef="c20220101to20220331_ProductOrServiceAxis_SpinrazaRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">53.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_24c482899718430ab80d1b8eea4f50c9" contextRef="c20210101to20210331_ProductOrServiceAxis_SpinrazaRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">60.0</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;">R&amp;D revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7b42b2f36432432293763a6f77f80ea0" contextRef="c20220101to20220331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">40.1</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5bf8b26d53bb4758a6849a5a518e9d5e" contextRef="c20210101to20210331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">18.1</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue from our relationship with Biogen</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6724abb5c13a4232947e36a5ec6e8a7f" contextRef="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">93.9</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;">&#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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_c129fb745a2941e19f25e008b752eba6" contextRef="c20210101to20210331_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">78.1</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%;"><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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_2378a184258a4c21b0f8a03a2ce4c8e8" contextRef="c20220101to20220331_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">66</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:ConcentrationRiskPercentage1" id="Fact_f9f72233c43a478a849fb1b7ab1a524e" contextRef="c20210101to20210331_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">70</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae13" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae14">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae14" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae15">
<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, 2022 and December 31, 2021<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="c20220331_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">385.5</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_7b83a105f51e48c19c4fa834b14d4660" contextRef="c20211231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">407.5</ix:nonFraction> million, respectively, related to our relationship with Biogen.</div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae15" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae16">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae16" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae17">
<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 quarter of 2022, we did not have any material changes to our performance obligations, transaction price or the timing in which we expect to recognize revenue under our Biogen collaborations.</div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae17" continuedAt="Text_a6516ca18f394caca18ab3f588bfb7ae18">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_a6516ca18f394caca18ab3f588bfb7ae18">
<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 2022, we earned $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ab91654b7168476fa5495fb1d76b719d" contextRef="c20210401to20210630_ProductOrServiceAxis_Ion541Member_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">18</ix:nonFraction> million in milestone payments from Biogen when Biogen advanced <ix:nonFraction name="ions:NumberOfTargetsAdvanced" id="Fact_92927dcd49a748aa867e72d5b5af4971" contextRef="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> targets under our 2013 strategic collaboration. We recognized the milestone payments in full in the first quarter of 2022 because we did not have any remaining performance obligations related to the milestone payments. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPotentialPayment" id="Fact_11c23dc721af4581b81256e8aebe8b08" contextRef="c20220331_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U002" decimals="-6" scale="6" format="ixt:numdotdecimal">10</ix:nonFraction> million if Biogen advances a medicine under our 2013 strategic neurology collaboration.</div>
</ix:continuation></div>
<div><br /></div>
<div><ix:nonNumeric name="us-gaap:DebtDisclosureTextBlock" id="Text_ef3a2cc101014877b712da5e56f03727" contextRef="c20220101to20220331" escape="true" continuedAt="Text_447fc7244e6947a48cc462680958b58c1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Convertible Debt</div>
</ix:nonNumeric><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c1" continuedAt="Text_447fc7244e6947a48cc462680958b58c2">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c2" continuedAt="Text_447fc7244e6947a48cc462680958b58c3">
<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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6084a279781c4f6f9d255000ab9021c3" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c3" continuedAt="Text_447fc7244e6947a48cc462680958b58c4">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c4" continuedAt="Text_447fc7244e6947a48cc462680958b58c5">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_31b7ba9c70ea47c98e3db30445a91628" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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_9dafbe4ac36f4acab7c5417e2b16fdb9" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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" 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="c20220331_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" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">257.0</ix:nonFraction> million.</div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c5" continuedAt="Text_447fc7244e6947a48cc462680958b58c6">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c6" continuedAt="Text_447fc7244e6947a48cc462680958b58c7"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_7221b32ba4b8461895c3e851d9ac7ed7" contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" escape="true" continuedAt="Text_77a8b7d0db7d4d9080d3d10890a84bf71">
<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, 2022, 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c7" continuedAt="Text_447fc7244e6947a48cc462680958b58c8"><ix:continuation id="Text_77a8b7d0db7d4d9080d3d10890a84bf71" continuedAt="Text_77a8b7d0db7d4d9080d3d10890a84bf72">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c8" continuedAt="Text_447fc7244e6947a48cc462680958b58c9"><ix:continuation id="Text_77a8b7d0db7d4d9080d3d10890a84bf72" continuedAt="Text_77a8b7d0db7d4d9080d3d10890a84bf73">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_edd5ff3b856642199ff86499cf0281a8" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" 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:DeferredFinanceCostsNet" id="Fact_8ceb1a5736644a6b89bc5c24ba652acf" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">12.6</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; background-color: #CCEEFF;"><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; 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;"><span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde">April 2026</span></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;"><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;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dce4bbae7b2a40908908ca4da1034984" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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; 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;">Effective 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:DebtInstrumentInterestRateEffectivePercentage" id="Fact_e393d99c85b54051913a784296da3887" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.5</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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c9" continuedAt="Text_447fc7244e6947a48cc462680958b58c10"><ix:continuation id="Text_77a8b7d0db7d4d9080d3d10890a84bf73">
<div><br /></div>
</ix:continuation></ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">23</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c10" continuedAt="Text_447fc7244e6947a48cc462680958b58c11">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a1c65db2db5e45bf9144abb23a3708cd" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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" 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" 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" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c11" continuedAt="Text_447fc7244e6947a48cc462680958b58c12">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c12" continuedAt="Text_447fc7244e6947a48cc462680958b58c13">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our 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>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c13" continuedAt="Text_447fc7244e6947a48cc462680958b58c14">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c14" continuedAt="Text_447fc7244e6947a48cc462680958b58c15">
<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_76ff515a60454ce18e1a9984840953ae" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction> Percent Convertible Senior Notes and Call Spread</div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c15" continuedAt="Text_447fc7244e6947a48cc462680958b58c16">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c16" continuedAt="Text_447fc7244e6947a48cc462680958b58c17"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_4533b9a35aa54a2d981119b07e67d99c" contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" escape="true" continuedAt="Text_babb2c7dbd0f46468ac29e8c7b75fc201">
<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, 2022, we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e999f0a79cc5454dbb35d79507c6bf14" contextRef="c20220331_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>
</ix:nonNumeric></ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c17" continuedAt="Text_447fc7244e6947a48cc462680958b58c18"><ix:continuation id="Text_babb2c7dbd0f46468ac29e8c7b75fc201" continuedAt="Text_babb2c7dbd0f46468ac29e8c7b75fc202">
<div><br /></div>
</ix:continuation></ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c18" continuedAt="Text_447fc7244e6947a48cc462680958b58c19"><ix:continuation id="Text_babb2c7dbd0f46468ac29e8c7b75fc202">
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td 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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9cc819b9413644d6b0245aee77431898" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_5b30f304e836422cb321c0bd36da9cea" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">548.8</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; width: 88%;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" 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:DeferredFinanceCostsNet" id="Fact_3f38f311c31c47e9afa1a4b179a0fa8a" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">6.0</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;"><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; 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;"><span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec">December 2024</span></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;"><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;">&#160;</td>
    <td colspan="2" valign="bottom" style="vertical-align: top;"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f28004647502413bae9a04a5c327033e" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:numdotdecimal">0.125</ix:nonFraction> percent</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;">Effective 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:DebtInstrumentInterestRateEffectivePercentage" id="Fact_a9ed75c8530a4cdd980eb1dc32b37ca0" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:numdotdecimal">0.5</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_6424592d0e3847f9b21c7950d9891db7" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:numdotdecimal">83.28</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_257883a038234987a42360f37188d9b5" contextRef="c20220331_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>
  </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_ed9c5d233d3b47b992cb88b28e7d96fe" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:numdotdecimal">6.6</ix:nonFraction></div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
</table>
</ix:continuation></ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c19" continuedAt="Text_447fc7244e6947a48cc462680958b58c20">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c20" continuedAt="Text_447fc7244e6947a48cc462680958b58c21">
<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><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fce48022202d43bb90824a8ab622ba1e" contextRef="c20220331_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="c20220331_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="c20220331_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="c20220331_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="c20220331_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="c20220331_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="c20220331_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="c20220331_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="c20220331_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="c20220331_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>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c21" continuedAt="Text_447fc7244e6947a48cc462680958b58c22">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c22" continuedAt="Text_447fc7244e6947a48cc462680958b58c23">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our 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>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c23" continuedAt="Text_447fc7244e6947a48cc462680958b58c24">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c24" continuedAt="Text_447fc7244e6947a48cc462680958b58c25">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fd23717a1d4d4ec2ae3decc69589c581" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction> Percent Convertible Senior Notes</div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c25" continuedAt="Text_447fc7244e6947a48cc462680958b58c26">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c26" continuedAt="Text_447fc7244e6947a48cc462680958b58c27">
<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 $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_5733913e61d243aba64ac5cdde17967a" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" 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="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $<ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_475d555508dd44ec879d8264ff4f449f" contextRef="c20210401to20210630_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">8.6</ix:nonFraction> million non-cash loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c7210172079a44a29a43562f67ccf9c3" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes. The non-cash loss on the early retirement of our debt is the difference between the amount paid to retire our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a41d730fa97348cbb6f1560579771061" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes and the net carrying balance of the liability at the time that we retired the debt. We paid the remaining principal balance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8adfad97b59c4a87a1edd27ef3c688bb" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes with $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_d0bfa204bf4c4321b5a5e9fcfe7261c1" contextRef="c20211101to20211130_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:numdotdecimal">62.0</ix:nonFraction> million of cash at maturity in November 2021.</div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c27" continuedAt="Text_447fc7244e6947a48cc462680958b58c28">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c28" continuedAt="Text_447fc7244e6947a48cc462680958b58c29">
<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>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c29" continuedAt="Text_447fc7244e6947a48cc462680958b58c30">
<div><br /></div>
</ix:continuation><ix:continuation id="Text_447fc7244e6947a48cc462680958b58c30">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b2fc1c75f5c641f2b66eff5bf9e11829" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">0</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c98e7aaf45cf42a78ac646beebca0a17" contextRef="c20220331_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 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 </span><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_537b73ba3c5546d3ac7077aac87f42f6" contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_34a97d073e54403cb2f896dd5cda4e81" contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">100</ix:nonFraction></ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.</span> The <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_be103130a6d84fa7b52179f2877f3f4e" contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:numdotdecimal">1</ix:nonFraction>% Notes were subject to similar terms.</div>
</ix:continuation></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">24</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 2</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 72pt">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">MANAGEMENT&#8217;S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Forward-Looking Statements</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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), eplontersen, olezarsen, donidalorsen, ION363, pelacarsen, tofersen 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, 2021, 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>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Overview"><!--Anchor--></a>Overview</div>
<div><br /></div>
<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 therapeutics. We believe our medicines have the potential to pioneer new markets, change standards of care and transform the lives of people with devastating diseases. We currently have three marketed medicines- SPINRAZA, TEGSEDI and WAYLIVRA. We also have a rich late-stage pipeline of medicines, primarily focused on our cardiovascular and neurology franchises. Our late-stage pipeline consists of six medicines in Phase 3 development for eight indications.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Our multiple sources of revenue and strong balance sheet enable us to invest in our strategic priorities to build our commercial pipeline, expand and diversify our technology and deliver new medicines to the market. By continuing to focus on these priorities, we believe we are well positioned to drive future growth and to deliver increasing value for patients and shareholders.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Marketed Medicines</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA is the global market leader for the treatment of patients 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, 2022, new patient starts in the U.S. reached a two-year high and initial uptake in China was strong as this was the first full quarter since receiving national reimbursement in China. Through March 31, 2022, we have earned more than $1.6 billion in revenues from our SPINRAZA collaboration, including more than $1.2 billion in royalties on sales of SPINRAZA.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI is a once weekly, self-administered subcutaneous medicine approved in the U.S., Europe, Canada and Brazil for the treatment of patients with polyneuropathy caused by hereditary polyneuropathy, or ATTRv-PN, 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 began distributing TEGSEDI in the U.S. and Canada. In Latin America, PTC Therapeutics International Limited, or PTC, is commercializing TEGSEDI in Brazil. PTC is pursuing access in additional Latin American countries under its exclusive license agreement with us. In the first quarter of 2022, we continued to progress into new and existing markets in Europe and Latin America through Sobi and PTC, respectively.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">25</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAYLIVRA is a once weekly, self-administered, subcutaneous medicine that received conditional marketing authorization in May 2019 from the European Commission, or EC, as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome, or FCS, and at high risk for pancreatitis. We launched WAYLIVRA in the EU in the third quarter of 2019. In 2021, we began selling WAYLIVRA in Europe through our distribution agreement with Sobi. Under our exclusive license agreement with PTC, PTC is working to provide access to WAYLIVRA across Latin America, beginning in Brazil. In the third quarter of 2021, the National Health Surveillance Agency (Ag&#234;ncia Nacional de Vigil&#226;ncia Sanit&#225;ria), or ANVISA, approved WAYLIVRA in Brazil. In December 2021, PTC submitted an application to ANVISA for approval of WAYLIVRA for the treatment of familial partial lipodystrophy, or FPL, in Brazil. If approved, Waylivra will be the first approved treatment for patients with FPL in Brazil.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi, we retained the marketing authorizations for TEGSEDI and WAYLIVRA in major markets. 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 and WAYLIVRA global commercial strategy. In connection with the agreements, we restructured our European operations in the first quarter of 2021, and we restructured our North American TEGSEDI operations in the second quarter of 2021.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Medicines in Phase 3 Studies</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We currently have six medicines in Phase 3 studies for eight indications, which include:</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">
  <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;">Eplontersen: our medicine in development for ATTR</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">
  <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;">In the second quarter of 2022, w</span>e achieved our original enrollment goal and increased the study size and duration in the Phase 3 CARDIO-TTRansform study in patients with ATTR cardiomyopathy, or ATTR-CM, with the aim to ensure a highly positive outcome and generate an even more robust data set to successfully compete in this growing and dynamic market. We expect data from this study in the first half of 2025</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">
  <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;">Enrollment is complete in the NEURO-TTRansform Phase 3 study in patients with ATTRv-PN. We expect data from this study in mid-2022</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">
  <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;">In the first quarter of 2022, the U.S. FDA granted orphan drug designation to eplontersen for the treatment of patients with ATTR</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">
  <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;">Olezarsen: our medicine in development for familial chylomicronemia syndrome, or FCS, and severe hypertriglyceridemia, or SHTG</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">
  <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;">Enrollment is ongoing in the BALANCE Phase 3 study in patients with FCS and the CORE Phase 3 study in patients with SHTG</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">
  <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;">We published positive data from the Phase 2 study of olezarsen in patients with hypertriglyceridemia and either at high risk for or with established cardiovascular disease in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">European Heart Journal</span></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">
  <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;">We initiated a study of olezarsen in patients with hypertriglyceridemia to support the broad Phase 3 program</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">
  <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;">Donidalorsen: our medicine in development for hereditary angioedema, or HAE</div></td>
  </tr>
</table>
<div style="text-align: justify; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">o</span><span style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#xA0;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Enrollment is ongoing in the Phase 3 OASIS-HAE study</span></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">
  <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;">We published positive data from the Phase 2 study of donidalorsen in patients with HAE in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">New England Journal of Medicine</span></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">
  <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;">We presented positive data from the Phase 2 study of donidalorsen in patients with HAE at the American Academy of Allergy, Asthma and Immunology annual meeting</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">
  <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;">ION363: our medicine in development for amyotrophic lateral sclerosis, or ALS, with mutations in the fused in sarcoma gene, or FUS. FUS-ALS is the most common cause of juvenile-onset ALS</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">
  <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;">Enrollment is ongoing in the Phase 3 study in patients with FUS-ALS</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">
  <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;">Pelacarsen: our medicine in development for lipoprotein(a), or Lp(a), driven cardiovascular disease</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">
  <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;">Enrollment is ongoing in Novartis&#8217; Lp(a) HORIZON Phase 3 cardiovascular outcome study in patients with established cardiovascular disease and elevated lipoprotein(a), or Lp(a)</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">
  <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;">Tofersen: our medicine in development for superoxide dismutase 1 ALS, or SOD1-ALS</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">
  <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;">Biogen plans to present new data from the ongoing VALOR open-label extension, or OLE, study at the European Network to Cure ALS meeting in June 2022</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">
  <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;">Biogen remains engaged with regulators to identify a potential path forward for tofersen</div></td>
  </tr>
</table>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">26</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">COVID-19</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a company focused on improving the health of people around the world, our priority during the COVID-19 pandemic 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 monitor the impact COVID-19 could have on our business, including the impact on our commercial products and the medicines in our pipeline.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Financial Highlights</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our financial results (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended 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;">2022</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;">2021</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;">&#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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">141.9</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">111.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">199.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">203.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss from operations</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(57.5</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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(92.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(65.2</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;">(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>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our financial results for the first quarter of 2022 reflected the cost-sharing provisions related to our eplontersen collaboration with AstraZeneca to develop and commercialize eplontersen for the treatment of ATTR. Under the terms of the collaboration agreement, AstraZeneca is paying 55 percent of the costs associated with the ongoing global Phase 3 development program. As we are leading the Phase 3 development program, we are recognizing as R&amp;D revenue the 55 percent of cost-share funding AstraZeneca is responsible for in the same period we incur the related development expenses. As a result of the cost-sharing provisions in our collaboration, we will receive payments of $20 million from AstraZeneca related to development expenses incurred in the first quarter of 2022.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As AstraZeneca is responsible for the majority of the medical affairs and commercial costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we are recognizing cost-share funding we receive from AstraZeneca related to these activities as a reduction of our medical affairs and commercialization expenses, which we classify as R&amp;D and SG&amp;A expenses, respectively. In the first quarter of 2022, we recognized $0.4 million and $0.2 million of medical affairs expenses and commercialization expenses for eplontersen, respectively, net of cost-share funding from AstraZeneca. We expect our medical affairs and commercialization expenses to increase as our collaboration with AstraZeneca progresses.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of the financial impacts on our statement of operations of the joint development activities under our eplontersen collaboration with AstraZeneca:</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;">
  <tr>
    <td style="width: 20.27%; 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;">Collaboration Activities</div></td>
    <td style="width: 1.52%; vertical-align: bottom;">&#160;</td>
    <td style="width: 19.97%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Financial Statement Line</div></td>
    <td style="width: 2.07%; vertical-align: bottom;">&#160;</td>
    <td colspan="3" style="width: 56.17%; 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;">Impact of Cost-Sharing Provisions on our Statement of Operations</div></td>
  </tr>
  <tr>
    <td rowspan="3" style="width: 20.27%; vertical-align: middle;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 Development:</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis leads and conducts</div></td>
    <td style="width: 1.52%; vertical-align: middle;">&#160;</td>
    <td style="width: 19.97%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen Joint Development Revenue</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(R&amp;D Revenue)</div></td>
    <td style="width: 2.07%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 7.02%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$20M</div></td>
    <td style="width: 1.38%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 47.77%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55% of Ionis&#8217; Phase 3 development expenses, including internal+external costs &amp; CMC costs</div></td>
  </tr>
  <tr>
    <td style="width: 1.52%; vertical-align: middle;">&#160;</td>
    <td style="width: 19.97%; vertical-align: middle;">&#160;</td>
    <td style="width: 2.07%; vertical-align: middle;">&#160;</td>
    <td style="width: 7.02%; vertical-align: middle;">&#160;</td>
    <td style="width: 1.38%; vertical-align: middle;">&#160;</td>
    <td style="width: 47.77%; vertical-align: middle;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 1.52%; vertical-align: middle;">&#160;</td>
    <td style="width: 19.97%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Development Expenses (R&amp;D expenses)</div></td>
    <td style="width: 2.07%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 7.02%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$36M</div></td>
    <td style="width: 1.38%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 47.77%; vertical-align: middle; background-color: #CCEEFF;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100% of Ionis&#8217; Phase 3 development expenses</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our revenue in the first quarter of 2022 increased more than 25 percent compared to the same period last year. The increase was driven by significant partner payments across multiple partnered programs, including $20 million from AstraZeneca for its share of the global Phase 3 program costs for eplontersen and $40 million from Biogen for advancing several neurology disease programs, including investigational medicines to treat patients with spinocerebellar ataxia type 3 and Parkinson&#8217;s disease, among others.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We completed the transition to Sobi of our TEGSEDI and WAYLIVRA commercial operations in Europe and our TEGSEDI commercial operations in North America in the first and second quarters of 2021, respectively. The decrease in TEGSEDI and WAYLIVRA revenue in the first quarter of 2022 compared to the same period last year was due to the shift from product sales to distribution fees based on net sales generated by Sobi. As part of the transition, we restructured our commercial operations in 2021, resulting in substantial cost savings.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">27</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses, excluding non-cash compensation expense related to equity awards, increased in the first quarter of 2022 compared to the same period in 2021. Our R&amp;D expenses increased due to our investments in advancing our late-stage pipeline, including our expanding number of Phase 3 studies, which doubled over the course of 2021 from three to six studies. Our SG&amp;A expenses included our investments in advancing our go-to-market activities for our near-term commercial opportunities. However, these expenses were offset by the savings we realized from the operating efficiencies we achieved from integrating Akcea and restructuring our commercial operations for TEGSEDI and WAYLIVRA. We expect our operating expenses, excluding non-cash compensation expense related to equity awards, to continue to increase during the rest of 2022 as we continue to build our commercial pipeline, invest in expanding and diversifying our technology and advance our go-to-market activities.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2022, we had $2.1 billion in cash and short-term investments and remain well capitalized with the resources we need to continue investing to drive future growth.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recent Business Updates</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">First Quarter 2022 Marketed Products Highlights</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA<sup>&#174;</sup>: the global market leader for the treatment of SMA patients of all ages</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">
  <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;">$473 million in worldwide SPINRAZA sales in the first quarter of 2022</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">
  <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;">Biogen provided updates from the ASCEND, RESPOND and NURTURE studies of SPINRAZA at the Muscular Dystrophy Association (MDA) Clinical and Scientific conference and the American Academy of Neurology (AAN) annual meeting</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI<sup>&#174;</sup> and WAYLIVRA<sup>&#174;</sup>: important medicines approved for the treatment of patients with polyneuropathy caused by hereditary TTR amyloidosis and familial chylomicronemia syndrome, respectively</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Continued to progress into new and existing markets in Europe and Latin America in the first quarter through Sobi and PTC, respectively</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 2022 and Recent Events</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Advancing our near-term commercial opportunities toward the market</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">
  <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;">Increased study size and duration in the Phase 3 CARDIO-TTRansform study of eplontersen in patients with ATTR-CM with the aim to generate even more robust data and ensure a highly positive study outcome to successfully compete in this growing and dynamic market. Data from this study are expected in the first half of 2025</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The U.S. FDA granted orphan drug designation to eplontersen for the treatment of patients with ATTR</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">
  <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;">Published positive data from the Phase 2 study of olezarsen in patients with hypertriglyceridemia and either at high risk for or with established cardiovascular disease in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">European Heart Journal</span></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">
  <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;">Initiated a study of olezarsen in patients with hypertriglyceridemia to support the broad Phase 3 program</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">
  <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;">Published positive data from the Phase 2 study of donidalorsen in patients with HAE in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">New England Journal of Medicine</span></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">
  <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;">Presented additional positive data from the Phase 2 study of donidalorsen in patients with HAE at the American Academy of Allergy, Asthma and Immunology annual meeting</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Advancing our leading cardiovascular disease franchise</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">
  <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;">AstraZeneca presented positive data from the Phase 2b ETESIAN study of ION449 (AZD8233) targeting PCSK9 in statin treated patients with dyslipidemia at the American College of Cardiology (ACC) annual scientific session</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">
  <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;">Achieved full enrollment in the Phase 2b study of IONIS-AGT-L<sub>Rx</sub> for patients with treatment-resistant hypertension, with data expected in the second half of 2022</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Advancing our leading neurological disease franchise</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">
  <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;">Roche plans to initiate a new Phase 2 study of tominersen in patients with Huntington&#8217;s disease based on findings from a post-hoc analysis of the GENERATION-HD1 study</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">
  <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;">Biogen initiated the Phase 1/2 study for ION260 (BIIB132) targeting ataxin-3 (ATXN3) in patients with spinocerebellar ataxia type 3 (SCA3), resulting in an $8 million milestone payment from Biogen</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">
  <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;">Biogen advanced the Phase 1/2 study for ION859 (BIIB094) targeting LRRK2 in patients with Parkinson&#8217;s disease, resulting in a $10 million milestone payment from Biogen</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">
  <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;">Announced the discontinuation of IONIS-C9<sub>Rx </sub>(BIIB078) due to lack of patient benefit demonstrated in the Phase 1/2 study in patients with C9orf72-ALS</div></td>
  </tr>
</table>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">28</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Business Segment</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a single segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.</div>
<div><br /></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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Assessing the propriety of revenue recognition and associated deferred revenue; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities</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;">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, 2021.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="ResultsofOperations"><!--Anchor--></a>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, 2022 was $141.9 million compared to $111.6 million for the same period in 2021 and was comprised of the following (amounts in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; 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;">53.8</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;">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%;"><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;">6.2</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;">19.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -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;">12.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">72.3</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;">84.4</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: 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;">17.4</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;">20.1</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;">27.2</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;">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>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">License fees</div></td>
    <td colspan="1" valign="bottom" 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;">2.0</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: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other services</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">1.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</div></td>
    <td colspan="1" valign="bottom" 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;">49.7</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;">27.2</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen joint development 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;">19.9</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;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: 27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27.2</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: 36pt; margin-left: 81pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">141.9</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;">111.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our revenue in the first quarter of 2022 increased more than 25 percent compared to the same period last year. The increase in our R&amp;D revenue was driven by significant partner payments across multiple partnered programs, including $20 million from AstraZeneca for its share of the global Phase 3 program costs for eplontersen and $40 million from Biogen for advancing several neurology disease programs, including investigational medicines to treat patients with spinocerebellar ataxia type 3 and Parkinson&#8217;s disease, among others.</div>
<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 2022 decreased compared to the same period last year. We completed the transition to Sobi of our TEGSEDI and WAYLIVRA commercial operations in Europe and our TEGSEDI commercial operations in North America in the first and second quarters of 2021, respectively. As a result of our distribution agreements with Sobi for TEGSEDI and WAYLIVRA, our commercial revenue from product sales shifted to commercial revenue from distribution fees based on net sales generated by Sobi. As part of the transition, we restructured our commercial operations in 2021, resulting in substantial cost savings.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">29</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">173.1</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;"><div style="font-family: '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>
  </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;">&#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>
    <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;">6.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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;">173.1</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;">165.7</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%; 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;">26.3</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;">37.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating 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;">199.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">203.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses, excluding non-cash compensation expense related to equity awards, for the three months ended&#xA0;March 31, 2022 increased compared to the same period in 2021. Our R&amp;D expenses increased due to our investments in advancing our late-stage pipeline, including our expanding number of Phase 3 studies, which doubled over the course of 2021 from three to six studies. Our SG&amp;A expenses included our investments to prepare for the launches of eplontersen, olezarsen and donidalorsen. However, these expenses were offset by the savings we realized from integrating Akcea and restructuring our TEGSEDI and WAYLIVRA commercial operations. 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 2022 as we continue to advance our mid- and late-stage medicines in development, invest in expanding and diversifying our technology and prepare for commercialization.</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.</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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">4.0</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;">2.4</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">4.2</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;">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>
  </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;"> increased slightly during the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in 2021.</span></div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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 style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">30</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on research, development and patent expenses (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">142.0</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;">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>
  </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;">&#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>
    <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;">2.6</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%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research, development and patent expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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;">142.0</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;">&#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;">113.9</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;">19.1</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;">25.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research, development and patent expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">161.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: 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: 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">19.1</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;"><div style="font-family: '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>
  </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;">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;">23.2</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;">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>
  </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;"> decreased in the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in 2021. In the first quarter of 2021, we incurred in-licensing expenses under our agreement with Genuity. We expect antisense drug discovery expenses to increase in the remainder of 2022 as we continue to invest in 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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 and WAYLIVRA</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;">2.1</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;"><div style="font-family: '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;">1.4</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;">Eplontersen</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;">27.0</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;">13.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olezarsen</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;">8.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.4</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;">Donidalorsen</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;">1.7</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;">1.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;"><div style="text-align: left; 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;">1.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">29.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.8</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;">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;">19.3</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;">18.3</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;">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;">&#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>
    <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>
  </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;">90.0</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;">&#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;">61.4</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;">8.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">98.6</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;">73.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> primarily due to our advancing late-stage pipeline, including our expanding number of Phase 3 studies, which doubled over the course of 2021 from three to six studies.</span></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">31</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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;">Medical Affairs</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our medical affairs function is responsible for communicating scientific and clinical information to healthcare providers, medical professionals and patients.</div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our medical affairs expenses were as follows (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">Medical affairs 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;">2.8</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;">2.9</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </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;">0.3</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%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total medical affairs expenses</div></td>
    <td 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;">3.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</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>
  </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;">Medical affairs expenses</span>, excluding non-cash compensation expense related to equity awards, were essentially flat in the three months ended&#xA0;March 31, 2022 compared to the same period in 2021. We expect medical affairs expenses to increase throughout 2022 as we advance our late-stage pipeline.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">16.3</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;">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>
  </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;">&#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>
    <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;">0.3</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%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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;">16.3</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;">12.1</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;">2.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total manufacturing and development chemistry expenses</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.0</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;">15.2</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>
  </tr>
</table>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">32</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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;"> increased in the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> due to increased costs we incurred in preparation for our near-term commercial launches, including manufacturing costs and activities for eplontersen and donidalorsen.</span></div>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">R&amp;D Support</span></div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our research, development and patent expenses, we include support costs such as rent, repair and maintenance for buildings and equipment, utilities, depreciation of laboratory equipment and facilities, amortization of our intellectual property, informatics costs, procurement costs and waste disposal costs. We call these costs R&amp;D support expenses.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on R&amp;D support expenses (in millions):</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">5.1</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;"><div style="font-family: '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;">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;">4.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.2</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%; 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;">0.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">0.9</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;">0.8</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;">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;">0.6</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;">&#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>
  </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;">2.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">13.8</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;">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>
  </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;">3.4</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;">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>
  </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;">17.2</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;">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>
  </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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> increased compared to the same period in </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The increase was primarily related to increased personnel and occupancy costs to support advancing our pipeline and our technology.</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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</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;">27.1</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;"><div style="font-family: '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>
  </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;">&#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>
    <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>
  </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;">27.1</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;">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>
  </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;">7.0</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 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;">34.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;"> decreased in the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>due to operating efficiencies achieved from the Akcea Merger and the restructuring of our commercial operations, partially offset by increased pre-commercialization expenses resulting from our go-to-market preparations for our near-term commercial opportunities. Non-cash compensation expense related to equity awards decreased in 2022 compared to 2021 due to reduced headcount as a result of the Akcea Merger and our restructured commercial operations.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">33</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">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, 2022 was $2.0 million compared to $4.6 million for the same period in 2021. Our investment income decreased because we earned a lower average return on our investments due to market conditions during the three months ended&#xA0;March 31, 2022 compared to the same period in 2021.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Interest Expense</div>
<div><br /></div>
<div style="text-align: 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"></div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
    <td colspan="6" valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">2022</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;">2021</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom;"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible 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;">1.3</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;">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>
  </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;">0.2</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;">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;">2.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over five years pursuant to IRC Section 174. Although the U.S. Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified. As a result, we recorded a $1.1 million income tax expense for the three months ended March 31, 2022, compared to $0.1 million for the same period in 2021.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Net Loss and Net Loss per Share</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We had a net loss of $65.2 million for the three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#xA0;</span>March 31, 2022 compared to net loss of $89.9 million for the same period in 2021, which reflects the fluctuations discussed above. Our b<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">asic 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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and 2021 were $</span>0.46<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and $</span>0.64<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively.</span></div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Liquidity"><!--Anchor--></a>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, 2022, we have earned approximately $6.0 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, 2022, we have raised net proceeds of approximately $2.0 billion from the sale of our equity securities. Additionally, from our inception through March 31, 2022, we have borrowed approximately $2.1 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 cash, cash equivalents and short-term investments, debt obligations and working capital did not change significantly from December 31, 2021 to </span>March 31, 2022.</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, 2022. The table provides a breakdown of when obligations become due. We provide a more detailed description of the major components of our debt in the paragraphs following the table:</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">34</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td 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; border-bottom: #000000 solid 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 % Notes (principal 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;">632.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 64%;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125% Notes (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">550.9</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;">0.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">550.2</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: 64%; background-color: #CCEEFF;"><div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building mortgage payments (principal and interest payable)</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; 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;">72.8</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;">3.0</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;">&#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;">69.8</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: 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;">26.6</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;">4.3</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;">22.3</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">&#160;</td>
  </tr>
  <tr>
    <td valign="bottom" style="vertical-align: bottom; width: 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;">0.8</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">0.7</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>
  </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;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,283.6</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">8.1</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;">&#160;</td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,275.5</div></td>
    <td colspan="1" valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 7, <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, 2022 for the purchase of services, capital equipment and materials as part of our normal course of business.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may enter into additional collaborations with partners which could provide for additional revenue to us and we may incur additional cash expenditures related to our obligations under any of the new agreements we may enter into. We currently intend to use our cash, cash equivalents and short-term investments to finance our activities. However, we may also pursue other financing alternatives, like issuing additional shares of our common stock, issuing debt instruments, refinancing our existing debt, or securing lines of credit. Whether we use our existing capital resources or choose to obtain financing will depend on various factors, including the future success of our business, the prevailing interest rate environment and the condition of financial markets generally.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">35</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div><a id="Item3MarketRisk"><!--Anchor--></a></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">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 3.</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-weight: bold;">QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are 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;">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. 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, 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>
<div><br /></div>
<div><a id="Item4Controls"><!--Anchor--></a></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">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 4.</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-weight: bold;">CONTROLS AND PROCEDURES</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We 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, 2022. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">There have been no significant changes in our internal controls or in other factors that could significantly affect internal controls subsequent to</span>&#xA0;March 31, 2022.</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>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTII"><!--Anchor--></a>PART II &#8212; OTHER INFORMATION</div>
<div><br /></div>
<div><a id="ITEM1"><!--Anchor--></a></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">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 1.</span></td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">LEGAL PROCEEDINGS</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;">From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If the potential loss from any legal proceeding is considered probable and the amount can be reasonably estimated, we accrue a liability for the estimated loss. Significant judgment is required to determine the probability of a loss and whether the amount of the loss is reasonably estimable. The outcome of any proceeding is not determinable in advance. As a result, the assessment of a potential liability and the amount of accruals recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding, and may revise our estimates.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">36</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On August 5, 2021, four purported former stockholders of Akcea filed an action in the Delaware Court of Chancery captioned John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. No. 2021-0681, or the &#8220;Delaware Action.&#8221;&#160; The plaintiffs in the Delaware Action assert claims against (i) former members of Akcea&#8217;s board of directors; and (ii) Ionis, or collectively, the &#8220;Defendants.&#8221; The plaintiffs assert putatively direct claims on behalf of a purported class of former Akcea stockholders. The plaintiffs in the Delaware Action assert that the Defendants breached their fiduciary duties in connection with the October 2020 take-private transaction that we and Akcea entered into, in which Akcea became a wholly-owned subsidiary of Ionis. We believe that the claims asserted in the Delaware Action are without merit and we filed a motion to dismiss the claims in November 2021. Briefing and argument on the motion to dismiss is complete and we are awaiting the court&#8217;s ruling on the motion.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">On January 19, 2022, a purported stockholder of Ionis filed a stockholder derivative complaint in the Delaware Court of Chancery captioned Leo Shumacher, et al. v. Joseph Loscalzo, et al., C.A. No. 2022-0059, or the &#8220;Action.&#8221; The complaint names as defendants the current members of Ionis&#8217; board of directors, collectively the &#8220;Directors&#8221;. The company is a nominal defendant. Plaintiff asserts a breach of fiduciary duty claim against the Directors for awarding and receiving allegedly excessive compensation. Plaintiff also asserts an unjust enrichment claim against the non-employee Directors as a result of the compensation they received. The complaint seeks, among other things, damages, restitution, attorneys&#8217; fees and costs, and such other relief as deemed just and proper by the court. The defendants have indicated they intend to file a motion to dismiss the claim, however no briefing schedule has been set.</div>
<div><br /></div>
<div><a id="ITEM1A"><!--Anchor--></a></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">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 1A.</span></td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">RISK FACTORS</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;">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, 2021.</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Summary of Risk Factors</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are a number of risks related to our business and our securities. Some of the principal risks related to our business include the following:</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the impact on our operations and financial condition from the effects of the current COVID-19 pandemic;</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to generate substantial revenue from the sale of our medicines;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our and our partners&#8217; ability to compete effectively;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the availability of adequate coverage and payment rates for our medicines;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to successfully manufacture our medicines;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to successfully develop and obtain marketing approvals for our medicines;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to secure and maintain effective corporate partnerships;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to sustain cash flows and achieve consistent profitability;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to protect our intellectual property;</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our ability to maintain the effectiveness of our personnel; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the other factors set forth below.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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>
<div><br /></div>
<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, 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 style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">37</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</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, in March 2020, we implemented work-from-home policies for most of our employees globally and generally suspended business-related travel.&#160; In the U.S., as vaccinations have become more widely available, states have lifted restrictions implemented as part of the pandemic response and reopened their economies. In June 2021, the Governor of California terminated the vast majority of executive actions that were put in place beginning in March 2020, leaving only a subset of provisions that facilitate the ongoing recovery. In May 2021, the Commonwealth of Massachusetts also lifted most of its pandemic restrictions. We continue to modify our policies for our employees in California, Massachusetts, and internationally to align with current local guidance.&#160; We believe the effects of these work-from-home and travel policies have had a limited impact on our business.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These public health directives and orders have 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 it is monitoring the demand for SPINRAZA, including the duration and degree to which it might see delays in starting new patients on SPINRAZA due to hospitals diverting resources necessary to administer SPINRAZA to care for COVID-19 patients. 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>
<div><br /></div>
<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.&#160; Recently there have been major disruptions to the global supply chain due to the COVID-19 Pandemic. To date, we have not experienced any significant consequences to our business as a result of the current supply chain disruptions, but could in the future if such disruptions persist or worsen.</div>
<div><br /></div>
<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>
<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">
  <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;">delays in clinical site initiation, site monitoring and patient enrollment due to restrictions imposed as a result of the COVID-19 Pandemic;</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">
  <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;">For example, in March 2020, we instituted a temporary suspension of enrollment for new subjects in our Phase 3 studies of eplontersen based on advice from our trial advisory committee; however, enrollment has resumed.</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">
  <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;">some patients have not been able to meet protocol requirements, as quarantines have impeded patient movement and interrupted healthcare services;</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">
  <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;">delays in site initiations due to principle investigators and site staff focusing on and prioritizing COVID-19 patient care; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">delays in necessary interactions with regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government or contractor personnel.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, some of our partners have experienced impacts to their clinical trial operations as a result of the COVID-19 Pandemic. For example, in December 2021, Novartis announced that enrollment for the Phase 3 HORIZON study had been delayed due to the COVID-19 Pandemic.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The spread of COVID-19 has caused a broad impact globally. While the potential economic impact brought by, and the duration of, the COVID-19 Pandemic may be difficult to assess or predict, it could result in significant disruption of global financial markets, reducing our ability to access capital, which could in the future negatively affect our liquidity. In addition, a recession or market correction resulting from the spread of COVID-19 could materially affect our business and has and could continue to affect the value of our securities.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The global COVID-19 Pandemic continues to rapidly evolve. While we have not yet experienced material adverse effects to our business as a result of the COVID-19 Pandemic, the ultimate impact of the COVID-19 Pandemic or a similar health epidemic is highly uncertain and subject to change. As such, we do not yet know the full extent of delays or impacts on our business, our clinical trials, healthcare systems or the global economy as a whole. However, these effects could have a material impact on our operations, and we will continue to monitor the COVID-19 Pandemic closely.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">38</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Commercialization 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 have limited experience as a company in commercializing medicines and we will have to invest significant resources to develop these capabilities. If we are unable to establish effective marketing, sales, market access, distribution, and related functions, or enter into agreements with third parties to commercialize our medicines, we may not be able to generate revenue from our medicines.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have limited experience as a company in commercializing medicines and we will have to invest significant financial and management resources to develop the infrastructure required to successfully commercialize our medicines. There are significant risks involved in building and managing a sales organization, including our ability to hire, retain and incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing personnel, and effectively manage a geographically dispersed sales and marketing team. We will also need to scale-up existing internal support functions to aid our commercialization efforts, in particular, regulatory affairs and medical affairs. Any failure to effectively build or maintain the infrastructure required to successfully commercialize our medicines, including our sales, marketing, market access, distribution, and related capabilities, or scale-up our existing support functions, could adversely impact the revenue we generate from our medicines. In addition, if we choose to rely on third parties to assist us in commercializing our medicines, we may not be able to enter into collaborations or hire consultants or external service providers on acceptable financial terms, or at all.&#160; If we do engage third parties to assist us in the commercialization of our medicines, our product revenues and profitability may be lower than if we commercialized such medicines ourselves.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the market does not accept our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, we are not likely to generate substantial revenues or become consistently profitable.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Even if our medicines are authorized for marketing, our success will depend upon the medical community, patients and third-party payers accepting our medicines as medically useful, cost-effective, safe and convenient. Even when the FDA or foreign regulatory authorities authorize our or our partners&#8217; medicines for commercialization, doctors may not prescribe our medicines to treat patients. Furthermore, we and our partners may not successfully commercialize additional medicines.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, in many of the markets where we or our partners may sell our medicines in the future, if we or our partners cannot agree with the government or other third-party payers regarding the price we can charge for our medicines, 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. If the pricing of any of our medicines decreases for any reason, it will reduce our revenue for such medicine. For example, Biogen has disclosed that SPINRAZA revenue has decreased in part due to lower pricing in the U.S. and certain rest of world markets.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The degree of market acceptance for our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, depends upon a number of factors, including the:</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">
  <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;">receipt and scope of marketing authorizations;</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">
  <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;">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>
  </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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cost and effectiveness of our medicines compared to other available therapies;</div></td>
  </tr>
</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">
  <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;">patient convenience of the dosing regimen for our medicines; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">reimbursement policies of government and third-party payers.</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;">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>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, TEGSEDI requires periodic blood and urine monitoring, is available in the U.S. only through a REMS program, and the product label in the U.S. has a boxed warning for thrombocytopenia and glomerulonephritis. Our main 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 nor is it available only through a REMS program. Additionally, the product label for WAYLIVRA in the EU requires regular blood monitoring. In each case, these label requirements have negatively affected our ability to attract and retain patients for these medicines. If we or our partner cannot effectively maintain patients on TEGSEDI or WAYLIVRA, including due to limitations or restrictions on the ability to conduct periodic blood and urine monitoring of our patients as a result of the current COVID-19 Pandemic, we may not be able to generate substantial revenue from TEGSEDI or WAYLIVRA sales.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">39</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we or our partners fail to compete effectively, our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, will not generate significant revenues.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our competitors engage in drug discovery throughout the world, are numerous, and include, among others, major pharmaceutical companies and specialized biopharmaceutical firms. Other companies are engaged in developing antisense technology. Our competitors may succeed in developing medicines that are:</div>
<div><br /></div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">priced lower than our medicines;</div></td>
  </tr>
</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">
  <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;">reimbursed more favorably by government and other third-party payers than our medicines;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">safer than our medicines;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">more effective than our medicines; or</div></td>
  </tr>
</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">more convenient to use than our medicines.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These competitive developments could make our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, obsolete or non-competitive.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others, including our competitors, to treat the same diseases our own collaborative programs target. Competition may negatively impact a partner&#8217;s focus on and commitment to our medicines and, as a result, could delay or otherwise negatively affect the commercialization of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Many of our competitors have substantially greater financial, technical and human resources than we do. In addition, many of these competitors have significantly greater experience than we do in conducting preclinical testing and human clinical studies of new pharmaceutical products, in obtaining FDA and other regulatory authorizations of such products and in commercializing such products. Accordingly, our competitors may succeed in obtaining regulatory authorization for products earlier than we do.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are several pharmaceutical and biotechnology companies engaged in the development or commercialization in certain geographic markets of products against targets that are also targets of products in our development pipeline. For example:</div>
<div><br /></div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;</div></td>
  </tr>
</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patisiran, tafamidis and tafamidis meglumine compete with TEGSEDI and could compete with eplontersen;</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Vutrisiran and acoramidis could compete with TEGSEDI and </span>eplontersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">;</span></div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">ARO-APOC3, lomitapide, evinacumab, BIO89-100, and gemcabene could compete with WAYLIVRA and olezarsen;</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">
  <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;">AMG890 could compete with pelacarsen;</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">
  <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;">Arimoclomol, ultomiris, mastinib and trehalose could compete with tofersen; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">Lanadelumab-flyo, C1 esterase inhibitor, berotralstat, C1 esterase inhibitor subcutaneous, garadacimab, KVD824, and NTLA-2002 could compete with donidalorsen.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA injection for intrathecal use is an antisense medicine indicated for the treatment of SMA patients of all ages approved in over 50 countries. Specifically, SPINRAZA faces competition from onasemnogene abeparvovec, a gene therapy product that was approved in the U.S. in May 2019 and in the EU in May 2020 for the treatment of SMA, as well as risdiplam, an oral product for the treatment of SMA that was approved in the U.S. in August 2020 and in the EU in March 2021. Biogen has disclosed that SPINRAZA revenue has decreased primarily due to a reduction in demand as a result of increased competition and that future sales of SPINRAZA may be adversely affected by competing products</span>.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, companies that are developing medicines that target the same patient populations as our medicines in development may compete with us to enroll participants in the clinical trials for such medicines, which could make it more difficult for us to complete enrollment for these clinical trials.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our medicines could be subject to regulatory limitations following approval.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Following approval of a medicine, we and our partners must comply with comprehensive government regulations regarding the manufacture, marketing and distribution of medicines. Promotional communications regarding prescription medicines must be consistent with the information in the product&#8217;s approved labeling. We or our partners may not obtain the labeling claims necessary or desirable to successfully commercialize our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">40</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and foreign regulatory bodies have the authority to impose significant restrictions on an approved medicine through the product label and on advertising, promotional and distribution activities. For example:</div>
<div><br /></div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in the U.S., TEGSEDI&#8217;s label contains a boxed warning for thrombocytopenia and glomerulonephritis;</div></td>
  </tr>
</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">
  <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;">TEGSEDI requires periodic blood and urine monitoring; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in the U.S., TEGSEDI is available only through a REMS program.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prescription medicines may be promoted only for the approved 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 uses may be subject to significant liability.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, when approved, the FDA or a foreign regulatory authority may condition approval on the performance of post-approval clinical studies or patient monitoring, which could be time consuming and expensive. For example, in connection with the conditional marketing approval for WAYLIVRA in the EU, we are required to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. If the results of such post-marketing studies are not satisfactory, the FDA, EC or other foreign regulatory authority may withdraw marketing authorization or may condition continued marketing on commitments from us or our partners that may be expensive and time consuming to fulfill.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or others identify side effects after any of our medicines are on the market, or if manufacturing problems occur subsequent to regulatory approval, or if we, our manufacturers or our partners fail to comply with regulatory requirements, we or our partners may, among other things, lose regulatory approval and be forced to withdraw products from the market, need to conduct additional clinical studies, incur restrictions on the marketing, distribution or manufacturing of the product, and/or change the labeling of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on our collaboration with Biogen for the development and commercialization of SPINRAZA.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into a collaborative arrangement with Biogen to develop and commercialize SPINRAZA. We entered into this collaboration primarily to:</div>
<div><br /></div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fund our development activities for SPINRAZA;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">seek and obtain regulatory approvals for SPINRAZA; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">successfully commercialize SPINRAZA.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA, generate additional clinical data for SPINRAZA, manufacture and 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>
<div><br /></div>
<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>
<div><br /></div>
<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>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on our collaboration with AstraZeneca for the joint development and commercialization of eplontersen.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into a collaborative arrangement with AstraZeneca to develop and commercialize eplontersen. Under the terms of the collaboration agreement, Ionis and AstraZeneca will co-develop and co-commercialize eplontersen in the U.S. and AstraZeneca will have the sole right to commercialize eplontersen in all other countries, except for certain Latin American countries. Prior to co-commercializing eplontersen in the U.S., we will need to negotiate a co-commercialization agreement with AstraZeneca to govern the parties&#8217; performance of co-commercialization, which agreement will include a commercial plan and budget. As a company we do not have experience with co-commercialization arrangements. We also do not have control over the amount and timing of resources that AstraZeneca devotes to our collaboration, particularly outside of the U.S. If the co-commercialization arrangement for eplontersen is not successful for any reason, eplontersen may not meet our commercial objectives and our revenues for eplontersen may be limited.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">41</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, a Joint Steering Committee, or JSC, having equal membership from us and AstraZeneca, and various subcommittees oversee and coordinate the development, manufacturing, commercialization and other exploitation activities for eplontersen in the U.S. by mutual agreement. If any subcommittee cannot reach unanimous agreement on any matter within its respective scope of authority, such matter may be referred to the JSC for resolution. If the JSC cannot come to a mutual agreement on any particular matter, this could delay our ability to develop or commercialize eplontersen.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are relying on third parties to market, sell and distribute TEGSEDI and WAYLIVRA.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have entered into agreements with third parties to commercialize TEGSEDI and WAYLIVRA as follows</span>:</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we entered into a distribution agreement with Sobi to commercialize TEGSEDI in the U.S. and Canada;</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we entered into a distribution agreement with Sobi to commercialize TEGSEDI and WAYLIVRA in Europe; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, we granted PTC the exclusive right to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on 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>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our operations are subject to additional healthcare laws.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our operations are subject to additional healthcare laws, including federal and state anti-kickback laws, false claims laws, transparency laws, such as the federal Sunshine Act, and health information privacy and security laws, which are subject to change at any time.&#160; For example, in November 2020, the U.S. Department of Health and Human Services issued a final rule modifying the anti-kickback law safe harbors for Medicare Part D plans, pharmacies, and pharmaceutical benefit managers. Efforts to ensure that our operations comply with current 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</span>.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If government or other third-party payers fail to provide adequate coverage and payment rates for our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development, our revenue will be limited.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In both domestic and foreign markets, sales of our current and future products will depend in part upon the availability of coverage and reimbursement from third-party payers. The majority of patients in the U.S. who would fit within our target patient populations for our medicines have their healthcare supported by a combination of Medicare coverage, other government health programs such as Medicaid, managed care providers, private health insurers and other organizations. Coverage decisions may depend upon clinical and economic standards that disfavor new medicines when more established or lower cost therapeutic alternatives are already available or subsequently become available. Assuming coverage is approved, the resulting reimbursement payment rates might not be enough to make our medicines affordable. Even if favorable coverage status and adequate reimbursement rates are attained, less favorable coverage policies and reimbursement rates may be implemented in the future. Accordingly, SPINRAZA, TEGSEDI and WAYLIVRA, 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>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">42</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Third-party payers, whether foreign or domestic, or governmental or commercial, are developing increasingly sophisticated methods of controlling healthcare costs. In addition, in the U.S., no uniform policy of coverage and reimbursement for medicines exists among third-party payers. Therefore, coverage and reimbursement for medicines can differ significantly from payer to payer. For example, the Affordable Care Act was passed in March 2010, and substantially changed the way healthcare is financed by both governmental and private insurers, and continues to significantly impact the U.S. pharmaceutical industry. There have been judicial and Congressional challenges to certain aspects of the Affordable Care Act, as well as efforts to repeal or replace certain aspects of the Affordable Care Act. It is unclear how future litigation and healthcare reform measures will impact the Affordable Care Act and our business.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Further, we believe that future coverage, reimbursement and pricing will likely be subject to increased restrictions both in the U.S. and in international markets. In the U.S., recent health reform measures have resulted in reductions in Medicare and other healthcare funding, and there have been several recent U.S. Congressional inquiries, legislation and executive orders designed to, among other things, reduce drug prices (e.g., by supporting drug price negotiation in Medicare Parts B and D, with those negotiated prices also available to commercial plans, and progressing legislation to slow price increases over time on existing drugs), increase competition (e.g., by supporting legislation to speed the entry of biosimilar and generic drugs, including shortening the period of exclusivity, policies in Medicare Part B to increase the prescribing of biosimilars by physicians, and a prohibition on &#8220;pay-for-delay&#8221; agreements and anti-competitive practices by drug manufacturers), lower out-of-pocket drug costs for patients (e.g., by capping Medicare Part D beneficiary out-of-pocket pharmacy expenses), and foster scientific innovation to promote better health care and improved health (e.g., by investing in public and private research and incentivizing the market to promote discovery of valuable and accessible new treatments). 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>
<div><br /></div>
<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>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To successfully commercialize any of our medicines, we 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 or the ongoing war between Russia and Ukraine, could limit the commercial success of our medicines. In addition, as our drug development and commercial pipeline increases and matures, we will have a greater need for clinical trial and commercial manufacturing capacity. For example, we have plans to expand our manufacturing infrastructure to support our wholly owned pipeline. If we are not successful in executing this expansion, it could limit our ability to meet our manufacturing requirements and commercial objectives in the future.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, we have limited experience manufacturing pharmaceutical products of the chemical class represented by our medicines, called oligonucleotides, on a commercial scale for the systemic administration of a medicine. There are a small number of suppliers for certain capital equipment and raw materials that we use to manufacture our medicines, and some of these suppliers will need to increase their scale of production to meet our projected needs for commercial manufacturing. Further, we must continue to improve our manufacturing processes to allow us to reduce our drug costs. We or our partners may not be able to manufacture our medicines at a cost or in quantities necessary to make commercially successful products.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">43</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Development and Regulatory Approval of our Medicines</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we or our partners fail to obtain regulatory approval for our medicines and additional approvals for SPINRAZA, TEGSEDI and WAYLIVRA, we or our partners cannot sell them in the applicable markets.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot guarantee that any of our medicines will be considered safe and effective or will be approved for commercialization. In addition, it is possible that SPINRAZA, TEGSEDI and WAYLIVRA may not be approved in additional markets or for additional indications. We and our partners must conduct time-consuming, extensive and costly clinical studies to demonstrate the safety and efficacy of each of our medicines before they can be approved or receive additional approvals for sale. We and our partners must conduct these studies in compliance with FDA regulations and with comparable regulations in other countries.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is possible that regulatory 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 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>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA or other comparable foreign regulatory authorities can delay, limit or deny approval of a medicine for many reasons, including:</div>
<div><br /></div>
<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">
  <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;">such authorities may disagree with the design or implementation of our clinical studies;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">we or our partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a medicine is safe and effective for any indication;</div></td>
  </tr>
</table>
<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">
  <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;">such authorities may not accept clinical data from studies conducted at clinical facilities that have deficient clinical practices or that are in countries where the standard of care is potentially different from the U.S.;</div></td>
  </tr>
</table>
<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">
  <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;">we or our partners may be unable to demonstrate that our medicine&#8217;s clinical and other benefits outweigh its safety risks to support approval;</div></td>
  </tr>
</table>
<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">
  <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;">such authorities may disagree with the interpretation of data from preclinical or clinical studies;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">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>
  </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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the approval policies or regulations of such authorities or their prior guidance to us or our partners during clinical development may significantly change in a manner rendering our clinical data insufficient for approval.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Failure to receive marketing authorization for our medicines, or failure to receive additional marketing authorizations for SPINRAZA, TEGSEDI or WAYLIVRA, or delays in these authorizations, could prevent or delay commercial introduction of the medicine, and, as a result, could negatively impact our ability to generate revenue from product sales.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We may not be able to benefit from orphan drug designation for our medicines.</div>
<div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br /></div>
<div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the U.S., under the Orphan Drug Act, the FDA may designate a medicine as an orphan drug if it is intended to treat a rare disease or condition affecting fewer than 200,000 individuals in the U.S. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process, but it can provide financial incentives, such as tax advantages and user-fee waivers, as well as longer regulatory exclusivity periods. The FDA has granted orphan drug designation to eplontersen for the treatment of patients with transthyretin-mediated amyloidosis. The FDA and EMA have granted orphan drug designation to TEGSEDI for the treatment of patients with ATTRv-PN, to WAYLIVRA for the treatment of patients with FCS, and to tominersen for the treatment of patients with HD. In addition, the EMA has granted orphan drug designation to WAYLIVRA for the treatment of patients with FPL. Even if approval is obtained on a medicine that has been designated as an orphan drug, we may lose orphan drug exclusivity if the FDA or EMA determines that the request for designation was materially defective or if we cannot assure sufficient quantity of the applicable medicine to meet the needs of patients with the rare disease or condition, or if a competitor is able to gain approval for the same medicine in a safer or more effective form or that makes a major contribution to patient care. If we lose orphan drug exclusivity on any of our medicines, we may face increased competition and lose market share for such medicine.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">44</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even if our medicines are successful in preclinical and human clinical studies, the medicines may not be successful in late-stage clinical studies.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Successful results in preclinical or initial human clinical studies, including the Phase 2 results for some of our medicines in development, may not predict the results of subsequent clinical studies. If any of our medicines in Phase 3 clinical studies, including the studies of eplontersen, olezarsen, donidalorsen, ION363, pelacarsen and tofersen, do not show sufficient efficacy in patients with the targeted indication, or if such studies are discontinued for any other reason, it could negatively impact our development and commercialization goals for these medicines and our stock price could decline.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the past, we have invested in clinical studies of medicines that have not met the primary clinical endpoints in their Phase 3 studies or have been discontinued for other reasons. For example, in October 2021, Biogen reported that tofersen did not meet the primary clinical endpoint in the Phase 3 VALOR study; however, trends favoring tofersen were seen across multiple secondary and exploratory measures of disease activity and clinical function. In addition, in March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest Huntington&#8217;s disease based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded Independent Data Monitoring Committee. Similar results could occur in clinical studies for our other medicines, including the studies of eplontersen, olezarsen, donidalorsen, ION363 and pelacarsen.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are a number of factors that could cause a clinical study to fail or be delayed, including:</div>
<div><br /></div>
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the clinical study may produce negative or inconclusive results;</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">
  <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;">regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">we, our partners, the FDA or foreign regulatory authorities could suspend or terminate a clinical study due to adverse side effects of a medicine on subjects or lack of efficacy in the trial;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">we, or our partners, may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">enrollment in our clinical studies may be slower than we anticipate;</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">
  <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;">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>
  </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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the institutional review board for a prospective site might withhold or delay its approval for the study;</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">
  <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;">enrollment in our clinical studies may be slower than we anticipate;</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">
  <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;">people who enroll in the clinical study may later drop out due to adverse events, a perception they are not benefiting from participating in the study, fatigue with the clinical study process or personal issues;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">a clinical study site may deviate from the protocol for the study;</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the cost of our clinical studies may be greater than we anticipate;</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">
  <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;">our partners may decide not to exercise any existing options to license and conduct additional clinical studies for our medicines; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.</div></td>
  </tr>
</table>
<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>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, our current medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, are chemically similar to each other. As a result, a safety observation we encounter with one of our medicines could have, or be perceived by a regulatory authority to have, an impact on a different medicine we are developing. This could cause the FDA or other regulators to ask questions or take actions that could harm or delay our ability to develop and commercialize our medicines or increase our costs. For example, the FDA or other regulatory agencies could request, among other things, 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 ongoing post-marketing studies for WAYLIVRA and TEGSEDI and an EAP for WAYLIVRA. Adverse events or results from these studies or the EAPs could negatively impact our pending or future marketing approval applications for WAYLIVRA and TEGSEDI in patients with FCS or ATTRv-PN, respectively, or the commercial opportunity for WAYLIVRA or TEGSEDI.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">45</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any failure or delay in our clinical studies, including the studies of tofersen, pelacarsen, eplontersen, olezarsen, donidalorsen, 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 Icon Clinical Research Limited, Syneos Health, Inc., Thermo Fisher Scientific Inc. and Medpace for the clinical studies for our medicines, including eplontersen, olezarsen, donidalorsen, ION363, pelacarsen and tofersen. We rely heavily on these parties for successful execution of our clinical studies, but do not control many aspects of their activities. For example, the investigators are not our employees. 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. For example, some of our key vendors are experiencing labor shortages, which could impact their ability to perform services for us for certain of our clinical trials. The failure of these third parties to carry out their obligations, including as a result of delays or 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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, while we do not have any clinical trial sites in Ukraine, we do have a limited number of clinical trial sites in Russia and surrounding countries that may be impacted by the ongoing war between Russia and Ukraine, and could result in difficulties enrolling or completing our clinical trials in such areas on schedule. Furthermore, the U.S. and its European allies have imposed significant new sanctions against Russia, including regional embargoes, full blocking sanctions, and other restrictions targeting major Russian financial institutions. The U.S. government has also indicated it will consider imposing additional sanctions and other similar measures in the near future. Our ability to conduct clinical trials in Russia may become restricted under applicable sanctions laws, which would require us to identify alternative trial sites, and could increase our costs and delay the clinical development of certain of our medicines.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Since corporate partnering is a significant part of our strategy to fund the advancement and commercialization of our development programs, if any of our collaborative partners fail to fund our collaborative programs, or if we cannot obtain additional partners, we may have to delay or stop progress on our drug development programs.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To date, corporate partnering has played a significant role in our strategy to fund our development programs and to add key development resources. We plan to continue to rely on additional collaborative arrangements to develop and commercialize 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>
<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">
  <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;">AstraZeneca for the joint development and funding of eplontersen;</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">
  <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;">Novartis for development and funding of pelacarsen;</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">
  <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;">Biogen for development and funding of tofersen; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">Roche for development and funding of tominersen.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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, after a review of data from the global Phase 2b study of vupanorsen, Pfizer decided to discontinue the clinical development program for vupanorsen.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">46</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even with funding from corporate partners, if our partners do not effectively perform their obligations under our agreements with them, it would delay or stop the progress of our drug development and commercial programs.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to receiving funding, we enter into collaborative arrangements with third parties to:</div>
<div><br /></div>
<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">
  <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;">conduct clinical studies;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">seek and obtain marketing authorizations; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">manufacture, market and sell our medicines.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Once we have secured a collaborative arrangement to further develop and commercialize one of our drug development programs, such as our collaborations with AstraZeneca, Bayer, Biogen, GSK, Novartis, and Roche, these collaborations may not continue or result in commercialized medicines, or may not progress as quickly as we first anticipated.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, a collaborator such as AstraZeneca, Bayer, Biogen, GSK, Novartis, or Roche, could determine that it is in its financial interest to:</div>
<div><br /></div>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">pursue alternative technologies or develop alternative products that may be competitive with the medicine that is part of the collaboration with us;</div></td>
  </tr>
</table>
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">pursue higher-priority programs or change the focus of its own development programs; or</div></td>
  </tr>
</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">
  <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;">choose to devote fewer resources to our medicines than it does for its own medicines.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If any of these occur, it could affect our partner&#8217;s commitment to the collaboration with us and could delay or otherwise negatively affect the commercialization of our medicines, including SPINRAZA, pelacarsen, tofersen, and eplontersen.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we do not progress in our programs as anticipated, the price of our securities could decrease.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For planning purposes, we estimate and may disclose the timing of a variety of clinical, regulatory and other milestones, such as when we anticipate a certain medicine will enter clinical trials, when we anticipate completing a clinical study, or when we anticipate filing an application for, or obtaining, marketing authorization, or when we or our partners plan to commercially launch a medicine. We base our estimates on present facts and a variety of assumptions, many of which are outside of our control, 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, eplontersen, olezarsen, donidalorsen, ION363, pelacarsen and tofersen, the price of our securities could decrease.</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Associated with our Businesses as a Whole</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our financial condition</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Because drug discovery and development requires substantial lead-time and money prior to commercialization, our expenses have generally exceeded our revenue since we were founded in January 1989. As of March 31, 2022, 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>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">47</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we fail to obtain timely funding, we may need to curtail or abandon some of our programs.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we had cash, cash equivalents and short-term investments equal to $</span>2.1<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>
<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">
  <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;">successful commercialization of SPINRAZA, TEGSEDI and WAYLIVRA;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">additional marketing approvals for WAYLIVRA and TEGSEDI;</div></td>
  </tr>
</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the profile and launch timing of our medicines, including eplontersen, olezarsen, donidalorsen, ION363, pelacarsen and tofersen;</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;</div></td>
  </tr>
</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">continued scientific progress in our research, drug discovery and development programs;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the size of our programs and progress with preclinical and clinical studies;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the time and costs involved in obtaining marketing authorizations;</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">competing technological and market developments, including the introduction by others of new therapies that address our markets; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">our manufacturing requirements and capacity to fulfill such requirements.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we need additional funds, we may need to raise them through public or private financing. Additional financing may not be available at all or on acceptable terms. If we raise additional funds by issuing equity securities, the shares of existing stockholders will be diluted and the price, as well as the price of our other securities, may decline. If adequate funds are not available or not available on acceptable terms, we may have to cut back on one or more of our research, drug discovery or development programs. Alternatively, we may obtain funds through arrangements with collaborative partners or others, which could require us to give up rights to certain of our technologies or medicines.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our intellectual property</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we cannot protect our patent rights or our other proprietary rights, others may compete more effectively against us.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our success depends to a significant degree upon whether we can continue to develop, secure and maintain intellectual property rights to proprietary products and services. However, we may not receive issued patents on any of our pending patent applications in the U.S. or in other countries and we may not be able to obtain, maintain or enforce our patents and other intellectual property rights which could impact our ability to compete effectively. In addition, the scope of any of our issued patents may not be sufficiently broad to provide us with a competitive advantage. Furthermore, other parties may successfully challenge, invalidate or circumvent our issued patents or patents licensed to us so that our patent rights do not create an effective competitive barrier or revenue source.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot be certain that the U.S. Patent and Trademark Office, or U.S. PTO, and courts in the U.S. or the patent offices and courts in foreign countries will consider the claims in our patents and applications covering SPINRAZA, TEGSEDI, WAYLIVRA, or any of our medicines in development as patentable. Method-of-use patents protect the use of a product for the specified method. This type of patent does not prevent a competitor from making and marketing a product that is identical to our product for an indication that is outside the scope of the patented method. Moreover, even if competitors do not actively promote their product for our targeted indications, physicians may prescribe these products off-label. Although off-label prescriptions may infringe or contribute to the infringement of method-of-use patents, the practice is common and such infringement is difficult to prevent, even through legal action.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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</span>.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">48</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intellectual property litigation could be expensive and prevent us from pursuing our programs.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we have to defend our intellectual property rights. If we are involved in an intellectual property dispute, we may need to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. PTO or the International Trade Commission or foreign patent authorities. Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If a third party claims that our medicines or technology infringe its patents or other intellectual property rights, we may have to discontinue an important product or product line, alter our products and processes, pay license fees or cease certain activities. We may not be able to obtain a license to needed intellectual property on favorable terms, if at all. There are many patents issued or applied for in the biotechnology industry, and we may not be aware of patents or patent applications held by others that relate to our business. This is especially true since patent applications in the U.S. are filed confidentially for the first 18 months. Moreover, the validity and breadth of biotechnology patents involve complex legal and factual questions for which important legal issues remain.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our personnel</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If our management transition is not successful our business could suffer.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2020, Dr. Crooke, our founder and Chief Executive Officer, transitioned from Chief Executive Officer to Executive Chairman of our Board of Directors, and Dr. Monia, who was our Chief Operating Officer and a member of our team since our founding over 30 years ago, began serving as our Chief Executive Officer. Following the 2021 Annual Meeting of Stockholders, Dr. Crooke stepped down from the Board and now serves as a Strategic Advisor to the Company, providing strategic advice and continuing to participate in the Company&#8217;s scientific activities. In June 2021, Dr. Loscalzo, a member of our Board since February 2014, was appointed Chairman of the Board. If this transition is not successful, our business could suffer.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The loss of key personnel, or the inability to attract and retain highly skilled personnel, could make it more difficult to run our business and reduce our likelihood of success.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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.</div>
<div><br /></div>
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to taxes</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our ability to use our net operating loss carryovers and certain other tax attributes may be limited.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the Internal Revenue Code of 1986, as amended, or the Code, a corporation is generally allowed a deduction for net operating losses, or NOLs, carried over from a prior taxable year. Under the Code, we can carryforward our NOLs to offset our future taxable income, if any, until such NOLs are used or expire. The same is true of other unused tax attributes, such as tax credits.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the current U.S. federal income tax law, U.S. federal NOLs generated in taxable years beginning after December 31, 2017 may be carried forward indefinitely, but the deductibility of such U.S. federal NOLs in taxable years beginning after December 31, 2020 is limited to 80 percent of taxable income. It is uncertain if and to what extent various states will conform to current U.S. federal income tax law, and there may be periods during which states suspend or otherwise limit the use of NOLs for state income tax purposes.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">49</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, under Sections 382 and 383 of the Code, and corresponding provisions of state law, if a corporation undergoes an &#8220;ownership change,&#8221; which is generally defined as a greater than 50 percentage-point cumulative change, by value, in its equity ownership over a three-year period, the corporation&#8217;s ability to use its pre-change NOL carryforwards and other pre-change tax attributes to offset its post-change income or taxes may be limited. We may experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. If an ownership change occurs and our ability to use our NOL carryforwards or other tax attributes is materially limited, it would harm our future operating results by effectively increasing our future tax obligations. As a result of the Akcea Merger, we are subject to the separate return limitation year, or SRLY, rules. Under the SRLY rules, our utilization of Akcea&#8217;s pre-merger NOL and tax credit carryforwards is limited to the amount of income that Akcea contributes to our consolidated taxable income. The Akcea pre-merger tax attributes cannot be used to offset any of the income that Ionis contributes to our consolidated taxable income. In addition, at the state level, there may be periods during which the use of net operating losses is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our future taxable income could be impacted by changes in tax laws, regulations and treaties.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A change in tax laws, treaties or regulations, or their interpretation, of any country in which we operate could materially affect us.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We could be subject to additional tax liabilities.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are subject to U.S. federal, state, local and foreign income taxes, sales taxes in the U.S., withholding taxes and transaction taxes in foreign jurisdictions. Significant judgment is required in evaluating our tax positions and our worldwide provision for taxes. During the ordinary course of business, there are many activities and transactions for which the ultimate tax determination is uncertain. In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax, accounting and other laws, regulations, principles and interpretations, including those relating to income tax nexus, by recognizing tax losses or lower than anticipated earnings in jurisdictions where we have lower statutory rates and higher than anticipated earnings in jurisdictions where we have higher statutory rates, by changes in foreign currency exchange rates, or by changes in the valuation of our deferred tax assets and liabilities. We may be audited in various jurisdictions, and such jurisdictions may assess additional taxes, sales taxes and value-added taxes against us. Although we believe our tax estimates are reasonable, the final determination of any tax audits or litigation could be materially different from our historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period for which a determination is made.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">General risk factors</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the price of our securities continues to be highly volatile, this could make it harder to liquidate your investment and could increase your risk of suffering a loss.*</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The market price of our common stock, like that of the securities of many other biopharmaceutical companies, has been and is likely to continue to be highly volatile. These fluctuations in our common stock price may significantly affect the trading price of our securities. During the 12 months preceding March 31, 2022, the market price of our common stock ranged from $47.87 to $25.04 per share. Many factors can affect the market price of our securities, including, for example, fluctuations in our operating results, announcements of collaborations, clinical study results, technological innovations or new products being developed by us or our competitors, the commercial success of our approved medicines, governmental regulation, marketing authorizations, changes in payers&#8217; reimbursement policies, developments in patent or other proprietary rights and public concern regarding the safety of our medicines.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Broad market factors may materially harm the market price of our common stock irrespective of our operating performance. For example, the current COVID-19 Pandemic has caused a significant disruption of global financial markets and has resulted in increased volatility in the trading price of our common stock. The global credit and financial markets may also be adversely affected by the ongoing war between Russia and Ukraine and measures taken in response thereto. In addition, industry factors may materially harm the market price of our common stock. NASDAQ, and the market for biotechnology companies in particular, have historically experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of the particular companies affected. The trading prices and valuations of these stocks, and of ours, may not be predictable. A loss of investor confidence in the market for biotechnology or pharmaceutical stocks or the stocks of other companies that investors perceive to be similar to us, the opportunities in the biotechnology and pharmaceutical market or the stock market in general, could depress our stock price regardless of our business, prospects, financial conditions or results of operations.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">50</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation provides for classified terms for the members of our board of directors. Our certificate also includes a provision that requires at least 66 2/3 percent of our voting stockholders to approve a merger or certain other business transactions with, or proposed by, any holder of 15 percent or more of our voting stock, except in cases where certain directors approve the transaction or certain minimum price criteria and other procedural requirements are met.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation 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>
<div><br /></div>
<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>
<div><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 0% Notes and used a portion of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million of our 1% Notes for $257.0 million. In December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our existing 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. Additionally, in connection with the pricing of our 0% Notes and 0.125% Notes, we entered into call spread transactions in which we purchased note hedges and sold warrants. Terminating or unwinding the call spread transactions could require us to make substantial payments to the counterparties under those agreements or may increase our stock price. The costs or any increase in stock price that may arise from terminating or unwinding such agreements could make an acquisition of our company significantly more expensive to the purchaser.</div>
<div><br /></div>
<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>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Future sales of our common stock in the public market could adversely affect the trading price of our securities.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Future sales of substantial amounts of our common stock in the public market, or the perception that such sales could occur, could adversely affect trading prices of our securities. For example, we may issue approximately 17.5 million shares of our common stock upon conversion of our 0% Notes and 0.125% Notes, up to 10.9 million shares in connection with the warrant transactions we entered into in connection with the issuance of our 0% Notes, and up to 6.6 million shares in connection with the warrant transactions we entered into in connection with the issuance of our 0.125% Notes, in each case subject to customary anti-dilution adjustments. The addition of any of these shares into the public market may have an adverse effect on the price of our securities.</div>
<div><br /></div>
<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>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">51</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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>
<div><br /></div>
<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>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are dependent on information technology systems, infrastructure and data, which exposes us to data security risks.*</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are dependent upon our own and third-party information technology systems, infrastructure and data, including mobile technologies, to operate our business. The multitude and complexity of our computer systems may make them vulnerable to service interruption or destruction, disruption of data integrity, malicious intrusion, or random attacks. Likewise, data privacy or security incidents or breaches by employees or others may pose a risk that sensitive data, including our intellectual property, trade secrets or personal information of our employees, patients, customers or other business partners may be exposed to unauthorized persons or to the public. Cyber-attacks are increasing in their frequency, sophistication and intensity, with third-party phishing and social engineering attacks in particular increasing during the COVID-19 Pandemic. In addition, the number and frequency of cybersecurity events globally may be heightened during times of geopolitical tension or instability between countries, including, for example, the ongoing war between Russia and Ukraine, as a result of which several companies (not including Ionis) have reported recent cybersecurity events.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cyber-attacks could include the deployment of harmful malware, denial-of-service, social engineering and other means to affect service reliability and threaten data confidentiality, integrity and availability. Our business partners face similar risks and any security breach of their systems could adversely affect our security posture. A security breach or privacy violation that leads to disclosure or modification of or prevents access to patient information, including personally identifiable information or protected health information, could harm our reputation, 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>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Because we use biological materials, hazardous materials, chemicals and radioactive compounds, if we do not comply with laws regulating the protection of the environment and health and human safety, our business could be adversely affected.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and manufacturing activities involve the use of potentially harmful biological materials as well as materials, chemicals and various radioactive compounds that could be hazardous to human health and safety or the environment. We store most of these materials and various wastes resulting from their use at our facilities in Carlsbad, California pending ultimate use and disposal. We cannot completely eliminate the risk of contamination, which could cause:</div>
<div><br /></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">
  <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;">interruption of our research, development and manufacturing efforts;</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">
  <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;">injury to our employees and others;</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">
  <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;">environmental damage resulting in costly clean up; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of these materials and resultant waste products.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In such an event, we may be held liable for any resulting damages, and any liability could exceed our resources. Although we carry insurance 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>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">52</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business may be adversely affected by climate change, extreme weather events, earthquakes, pandemics, war, civil or political unrest, terrorism or other catastrophic events.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In recent years, extreme weather events and changing weather patterns have become more common. As a result, we are potentially exposed to varying natural disaster or extreme weather risks such as hurricanes, tornadoes, fires, droughts, floods, or other events that may result from the impact of climate change on the environment. The potential impacts of climate change may also include increased operating costs associated with additional regulatory requirements and investments in reducing energy, water use and greenhouse gas emissions. In addition, we 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 disasters or other events outside our control, such as earthquakes, pandemics, war, civil or political unrest, deliberate acts of sabotage, terrorism or industrial accidents such as fire and explosion, whether due to human or equipment error, and if such facilities are affected by a disaster or other event, our development and commercialization efforts would be delayed. Although we possess property damage and business interruption insurance coverage, this insurance may not be sufficient to cover all of our potential losses and may not continue to be available to us on acceptable terms, or at all. In addition, our development and commercialization activities could be harmed or delayed by a shutdown of the U.S. government, including the FDA.</div>
<div><br /></div>
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business is subject to changing regulations for corporate governance and public disclosure that has increased both our costs and the risk of noncompliance.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Each year we are required to evaluate our internal control systems 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 have recently experienced substantial turmoil and uncertainty characterized by unprecedented intervention by the U.S. federal government in response to the COVID-19 Pandemic. In addition, the global credit and financial markets may be adversely affected by the ongoing war between Russia and Ukraine and measures taken in response thereto. In the past, the failure, bankruptcy, or sale of various financial and other institutions created similar turmoil and uncertainty in such markets and industries. It is possible that a 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. In addition, due to the rapidly rising inflation rate, we may experience increased costs of goods and services for our business.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">53</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A variety of risks associated with operating our business and marketing our medicines internationally could adversely affect our business. In addition to our U.S. operations, we are commercializing TEGSEDI in the EU, Canada, Latin America and certain Caribbean countries, and WAYLIVRA in the EU, Latin America and certain Caribbean countries. We face risks associated with our international operations, including possible unfavorable regulatory, pricing and reimbursement, political, tax and labor conditions, which could harm our business. Because we have international operations, we are subject to numerous risks associated with international business activities, including:</div>
<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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with differing or unexpected regulatory requirements for our medicines and foreign employees;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;</div></td>
  </tr>
</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">difficulties in staffing and managing foreign operations;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in certain circumstances, increased dependence on the commercialization efforts and regulatory compliance of third-party distributors or strategic partners;</div></td>
  </tr>
</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">foreign government taxes, regulations and permit requirements;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">U.S. and foreign government tariffs, trade restrictions, price and exchange controls and other regulatory requirements;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <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;">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>
  </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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenue, and other obligations related to doing business in another country;</div></td>
  </tr>
</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">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;</div></td>
  </tr>
</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">
  <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;">workforce uncertainty in countries where labor unrest is more common than in the U.S.; and</div></td>
  </tr>
</table>
<table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0">
  <tr>
    <td style="width: 36pt;"></td>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in diplomatic and trade relationships.</div></td>
  </tr>
</table>
<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 signed in December 2020.</div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">54</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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</span>.</div>
<div><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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</span>.</div>
<div><br /></div>
<div><a id="ITEM2"><!--Anchor--></a></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">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 2.</span></td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS</div></td>
  </tr>
</table>
<div><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>
<div><br /></div>
<div><a id="ITEM3"><!--Anchor--></a></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">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 3.</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-weight: bold;">DEFAULT UPON SENIOR SECURITIES</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;">Not applicable.</div>
<div><br /></div>
<div><a id="ITEM4"><!--Anchor--></a></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">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 4.</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-weight: bold;">MINE SAFETY DISCLOSURES</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;">Not applicable.</div>
<div><br /></div>
<div><a id="ITEM5"><!--Anchor--></a></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">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 5.</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-weight: bold;">OTHER 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;">Not applicable.</div>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">55</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div><a id="ITEM6"><!--Anchor--></a></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">
  <tr>
    <td style="width: 72pt; vertical-align: top; align: right;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 6.</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-weight: bold;">EXHIBITS</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">
  <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;">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>
  </tr>
</table>
<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;">
  <tr>
    <td style="width: 8.46%; 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: 1.5%; vertical-align: top;">&#160;</td>
    <td style="width: 90.04%; 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>
  </tr>
  <tr>
    <td style="width: 8.46%; 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="ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1</a></div></td>
    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amended and Restated Ionis Pharmaceuticals, Inc. Severance Benefit Plan.</div></td>
  </tr>
  <tr>
    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.46%; 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="ex31_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.1</a></div></td>
    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification by Chief Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.</div></td>
  </tr>
  <tr>
    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.46%; 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="ex31_2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.2</a></div></td>
    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification by Chief Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.</div></td>
  </tr>
  <tr>
    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.46%; 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="ex32_1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32.1</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div></td>
    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.</div></td>
  </tr>
  <tr>
    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.46%; 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>
    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following financial statements from the Ionis Pharmaceuticals, Inc. Quarterly Report on Form 10-Q for the quarter ended March 31, 2022, formatted in Inline Extensible Business Reporting Language (iXBRL): (i) condensed consolidated balance sheets, (ii) condensed consolidated statements of operations, (iii) condensed consolidated statements of comprehensive income (loss), (iv) condensed consolidated statements of stockholders&#8217; equity, (v) condensed consolidated statements of cash flows and (vi) notes to condensed consolidated financial statements (detail tagged).</div></td>
  </tr>
  <tr>
    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 8.46%; 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;">104</div></td>
    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>
    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cover Page Interactive Data File (formatted in iXBRL and included in exhibit 101).</div></td>
  </tr>
</table>
<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">
  <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;">This certification is deemed not filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended.</div></td>
  </tr>
</table>
<div><br /></div>
<div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="DSPFPageBreakArea">
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">56</span></div>
</div>
<div style="page-break-after:always;" class="DSPFPageBreak"><hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>
<div class="DSPFPageHeader">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a href="#Index" style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Index</a></div>
</div>
</div>
<div><br /></div>
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="SIGNATURES"><!--Anchor--></a>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>
<table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 27.57%; 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;">Signatures</div></td>
    <td style="width: 2.19%; vertical-align: bottom;">&#160;</td>
    <td style="width: 50.36%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div></td>
    <td style="width: 2.15%; vertical-align: bottom;">&#160;</td>
    <td style="width: 17.72%; vertical-align: bottom; border-bottom: #000000 2px solid;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Date</div></td>
  </tr>
  <tr>
    <td style="width: 27.57%; vertical-align: top;">&#160;</td>
    <td style="width: 2.19%; vertical-align: bottom;">&#160;</td>
    <td style="width: 50.36%; vertical-align: top;">&#160;</td>
    <td style="width: 2.15%; vertical-align: bottom;">&#160;</td>
    <td style="width: 17.72%; vertical-align: top;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 27.57%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ BRETT P. MONIA</div></td>
    <td rowspan="2" style="width: 2.19%; vertical-align: bottom;">&#160;</td>
    <td style="width: 50.36%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director and Chief Executive Officer</div></td>
    <td rowspan="2" style="width: 2.15%; vertical-align: bottom;">&#160;</td>
    <td style="width: 17.72%; vertical-align: bottom;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 27.57%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div></td>
    <td style="width: 50.36%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Principal executive officer)</div></td>
    <td style="width: 17.72%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">May 4, 2022</div></td>
  </tr>
  <tr>
    <td style="width: 27.57%; vertical-align: top;">&#160;</td>
    <td style="width: 2.19%; vertical-align: bottom;">&#160;</td>
    <td style="width: 50.36%; vertical-align: top;">&#160;</td>
    <td style="width: 2.15%; vertical-align: bottom;">&#160;</td>
    <td style="width: 17.72%; vertical-align: bottom;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 27.57%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div></td>
    <td rowspan="2" style="width: 2.19%; vertical-align: bottom;">&#160;</td>
    <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>
    <td rowspan="2" style="width: 2.15%; vertical-align: bottom;">&#160;</td>
    <td style="width: 17.72%; vertical-align: bottom;">&#160;</td>
  </tr>
  <tr>
    <td style="width: 27.57%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elizabeth L. Hougen</div></td>
    <td style="width: 50.36%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Principal financial and accounting officer)</div></td>
    <td style="width: 17.72%; vertical-align: bottom;"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">May 4, 2022</div></td>
  </tr>
</table>
<div><br /></div>
<div class="DSPFPageFooter">
<div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span class="DSPFPageNumber">57</span></div>
</div>
</body>
</html>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-10.1
<SEQUENCE>2
<FILENAME>ex10-1.htm
<DESCRIPTION>EXHIBIT 10.1
<TEXT>
<html>
  <head>
    <title></title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using EDGARfilings PROfile 8.2.0.0
         Copyright 1995 - 2022 Broadridge -->
  </head>
<body bgcolor="#ffffff" style="font-family: 'Times New Roman'; font-size: 10pt; text-align: left; color: #000000;">
  <!--PROfilePageNumberReset%Num%1%- % -%-->
  <hr noshade="noshade" align="center" style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;">
  <div style="font-weight: bold; text-align: right;">Exhibit 10.1<br>
  </div>
  <div>
    <div><br>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Amended and Restated</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><a name="z_DV_M1"></a>Severance Benefit Plan</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M2"></a><a name="z_Ref296430653"></a><font style="font-weight: bold;">1.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Introduction</font><font style="font-weight: bold;">. </font>This

      Amended and Restated Ionis Pharmaceuticals, Inc. Severance Benefit Plan (the &#8220;<font style="font-weight: bold; font-style: italic;">Plan</font>&#8221;) is adopted by Ionis Pharmaceuticals, Inc. (the &#8220;<font style="font-weight: bold; font-style: italic;">Company</font>&#8221;)

      on March 17, 2022 (the &#8220;<font style="font-weight: bold; font-style: italic;">Effective Date</font>&#8221;) and amends and restates the Severance Benefit Plan established by the Company on October 18, 2018. The Plan provides for severance benefits to
      selected employees of the Company. This document constitutes the Summary Plan Description for the Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M4"></a><font style="font-weight: bold;">2.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-weight: bold; font-variant: small-caps;">Definitions</font><font style="font-weight: bold;">. </font>For purposes of the
      Plan, the following terms are defined as follows:</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M5"></a><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Affiliate</font>&#8221; shall have the meaning given to such term in the
      Equity Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160; &#160; &#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Board</font>&#8221; means the Board of Directors of the Company.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M6"></a><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#8220;<font style="font-weight: bold; font-style: italic;">Cause</font>&#8221; means the occurrence of any one or more of the
      following: (i) any material breach of any written agreement between the Participant and the Company, if such breach causes material harm to the Company or reasonably threatens to cause such harm; (ii) any material failure to comply with the Company&#8217;s
      written policies or rules, as they may be in effect from time to time during the Participant&#8217;s employment or any statutory duty to the Company, if such failure causes material harm to the Company or reasonably threatens to cause such harm, and to the
      extent it is curable by the Participant, is not cured within 30 days after written notice thereof is given to the Participant by the Company; (iii) commission, conviction of, or a plea of &#8220;guilty&#8221; or &#8220;no contest&#8221; to, a felony under the laws of the
      United States or any State; or (iv) any willful, intentional or grossly negligent act having the effect of materially injuring (whether financially or otherwise) the business or reputation of the Company, which to the extent it is curable by the
      Participant, is not cured within 30 days after written notice thereof is given to the Participant by the Company.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M7"></a><font style="font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160; &#160;&#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Change in Control</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">CiC</font>&#8221; for purposes of this Plan shall mean the sale of all or substantially all the assets of the Company; any merger, consolidation or acquisition of the Company with, by or into another corporation, entity or person; or
      any change in the ownership of more than 50% of the voting capital stock of the Company in one or more related transactions, <font style="font-style: italic;">provided</font>, none of the following events will be a Change in Control: (1)
      acquisitions of capital stock directly from the Company for cash, whether in a public or private offering, (2) distributions of capital stock by the Company&#8217;s stockholders, (3) acquisitions of capital stock by or from any employee benefit plan or
      related trust, or (4) a merger for which the sole purpose is to change the Company&#8217;s name and/or state of incorporation.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M13"></a><font style="font-weight: bold;">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Change in Control Protection Period</font>&#8221; means the period
      commencing three months prior to, and ending 12 months following, the effective date of a Change in Control.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(f)</font>&#160;&#160;&#160;&#160;&#160; &#160; &#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Change in Control Termination</font>&#8221; means a Participant&#8217;s Qualifying Termination that
      occurs during the Change in Control Protection Period.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 1 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M14"></a><font style="font-weight: bold;">(g)</font>&#160;&#160; &#160;&#160; &#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">CiC Severance Period</font>&#8221; means the number of months of severance
      payable under this Plan to the Participant with respect to the applicable Change in Control Termination, as indicated in the Participant&#8217;s Participation Notice, which will be (i) 24 months for the Chief Executive Officer,&#160; (ii) 18 months for
      Executive Vice Presidents, (iii) 12 months for Senior Vice Presidents, and (iv) 9 months for Vice Presidents.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(h)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Code</font>&#8221; means the Internal Revenue Code of 1986, as amended.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M15"></a><font style="font-weight: bold;">(i)</font>&#160;&#160;&#160;&#160;&#160; &#160; &#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Common Stock</font>&#8221; means the common stock of the Company.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M16"></a><a name="z_DV_M17"></a><font style="font-weight: bold;">(j)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Continuous Service</font>&#8221; shall have the
      meaning given to such term in the Equity Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(k)</font>&#160;&#160;&#160;&#160; &#160; &#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Disability</font>&#8221; shall have the meaning given to such term in the Equity Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(l)</font>&#160;&#160;&#160;&#160; &#160; &#160; &#160;&#160; <font style="font-weight: bold; font-style: italic;">&#8220;Employment Agreement&#8221; </font>means<font style="font-weight: bold; font-style: italic;">&#160;</font>any


      individual employment offer letter, contract or agreement that a Participant has with the Company.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(m)</font>&#160;&#160;&#160;&#160; &#160; &#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Equity Award</font>&#8221; means each compensatory equity award granted to a Participant, whether
      under the Equity Plan, or otherwise.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(n)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Equity Plan</font>&#8221; means the Company&#8217;s 2011 Equity Incentive Plan or the Company&#8217;s 2020
      Equity Incentive Plan, as applicable, in each case as amended from time to time.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(o)</font>&#160;&#160;&#160;&#160;&#160; &#160; &#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">ERISA</font>&#8221; means the Employee Retirement Income Security Act of 1974, as amended.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M18"></a><font style="font-weight: bold;">(p)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Good Reason</font>&#8221; means the occurrence of any of the following
      events without the Participant&#8217;s consent: (i) a material reduction by the Company of the Participant&#8217;s base salary as in effect immediately prior to the reduction; (ii) a material reduction by the Company of the Participant&#8217;s annual bonus target as
      in effect immediately prior to the reduction, provided a compensation plan change that affects similarly all employees at similar levels will not constitute Good Reason; (iii) a material reduction in the Participant&#8217;s authority, duties or
      responsibilities, provided a change in job title or reporting relationship without a reduction in the Participant&#8217;s base salary or annual bonus target will not constitute Good Reason; or (iv) relocation of the offices at which the Participant is
      required to work to a location that is outside San Diego county or would increase the Participant&#8217;s one-way commute by more than 40 miles;<font style="font-style: italic;"> provided</font>, that any resignation by the Participant due to any of the
      above conditions will only be deemed for Good Reason if: (1) the Participant gives the Company written notice of the intent to terminate for Good Reason within 90 days following the first occurrence of the condition(s) that the Participant believes
      constitutes Good Reason, which notice will describe such condition(s); (2) the Company fails to remedy, if remediable, such condition(s) within 30 days following receipt of the Participant&#8217;s written notice (the &#8220;<font style="font-weight: bold; font-style: italic;">Cure Period</font>&#8221;) of such condition(s) from the Participant; and (3) the Participant actually resigns his or her employment within the first 15 days after expiration of the Cure Period.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(q)</font>&#160;&#160;&#160; &#160; &#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Individual Severance Arrangement</font>&#8221; means any Employment Agreement providing for
      severance or change in control benefits to a Participant or any other severance arrangement between the Participant and the Company other than the Plan, in each case that remains in effect through the date of a Qualifying Termination.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 2 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(r)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Non-CiC</font>&#160;<font style="font-weight: bold; font-style: italic;">Severance Period</font>&#8221;
      means the number of months of severance payable under this Plan to the Participant with respect to the applicable Non-CiC Termination, as indicated in the Participant&#8217;s Participation Notice, which will be (i) 18 months for the Chief Executive
      Officer, (ii) 12 months for Executive Vice Presidents, (iii) 9 months for Senior Vice Presidents, and (iv) 6 months for Vice Presidents.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(s)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Non-CiC Termination</font>&#8221; means a Participant&#8217;s Qualifying Termination that does not
      occur during the Change in Control Protection Period.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(t)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#8220;<font style="font-weight: bold; font-style: italic;">Participant</font>&#8221; means each individual who is employed by the Company, has been
      designated as a Participant by the Plan Administrator, and has received and returned a signed Participation Notice.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M21"></a><font style="font-weight: bold;">(u)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Participation Notice</font>&#8221; means the latest notice delivered by the
      Company to a Participant informing the Participant that he or she is eligible to participate in the Plan, substantially in the form attached hereto as <font style="font-weight: bold; font-variant: small-caps;">Exhibit A</font>.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M22"></a><font style="font-weight: bold;">(v)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Plan Administrator</font>&#8221; means the Board or any committee of the
      Board duly authorized to administer the Plan, including the Compensation Committee of the Board, or any member of senior management of the Company designated by the Board (including, for example, the head of Human Resources). The Board may at any
      time administer the Plan, in whole or in part, notwithstanding that the Board has previously appointed a committee or other person to act as the Plan Administrator. Notwithstanding the foregoing, upon and after the consummation of a Change in
      Control, the Plan Administrator shall mean the Representative.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(w)</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-weight: bold; font-style: italic;">&#8220;Person&#8221;</font> means a &#8220;person&#8221; as such term is used in Sections 13(d) and 14(d) of the
      United States Securities Exchange Act of 1934, as amended</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M23"></a><a name="z_DV_M24"></a><font style="font-weight: bold;">(x)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Pro-rated Target Bonus</font>&#8221; means with
      respect to a Participant, the portion of the Participant&#8217;s target annual bonus under the Company&#8217;s annual cash bonus plan or policy then in effect (and without giving effect to any reduction in target bonus that would give rise to the Participant&#8217;s
      right to resign for Good Reason) pro-rated based on the number of days from the beginning of the calendar year through the date of the Participant&#8217;s Non-CiC Termination.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(y)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#8220;<font style="font-weight: bold; font-style: italic;">Qualifying Termination</font>&#8221; means a termination of the Participant&#8217;s Continuous Service
      either (i) by the Company without Cause or (ii) by the Participant with Good Reason.&#160; Termination of Continuous Service due to the Participant&#8217;s death or Disability will not constitute a Qualifying Termination.&#160; Transferring from the Company to an
      Affiliate where such transfer does not constitute Good Reason will not constitute a Qualifying Termination.&#160; For clarity, if the Participant terminates his or her employment without Good Reason, and the Company unilaterally accelerates the
      Participant&#8217;s date of termination in connection therewith, such acceleration will not result in a termination by the Company without Cause or a Qualifying Termination hereunder.&#160; Further, if the Participant is offered an identical or substantially
      equivalent or comparable position with the Company or an Affiliate, such Participant will not be deemed to have been terminated without Cause.&#160; For purposes of the foregoing, a &#8220;substantially equivalent or comparable position&#8221; is one that provides
      the Participant substantially the same level of responsibility and compensation.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 3 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(z)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Release Effective Date</font>&#8221; means the date, which must occur during the Release Period,
      on which the Release becomes effective and is no longer revocable by the Participant.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(aa)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Release</font>&#8221; has the meaning set forth in Section 6.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(bb)</font>&#160;&#160;&#160;&#160; &#160; &#160; &#8220;<font style="font-weight: bold; font-style: italic;">Release Period</font>&#8221; means the sixty-day period following a Participant&#8217;s Qualifying
      Termination during which the Release must be executed (and not revoked) by the Participant.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(cc)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Representative</font>&#8221; means one or more members of the Board or other persons designated by
      the Board (including a member of senior management such as the head of Human Resources) prior to or in connection with a Change in Control to administer the Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(dd)</font>&#160;&#160; &#160;&#160; &#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Separation from Service</font>&#8221; means a &#8220;separation from service&#8221; within the meaning of
      Treasury Regulations Section 1.409A-1(h), without regard to any alternative definition thereunder.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(ee)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Target Bonus</font>&#8221; means with respect to a Participant, 100% of the Participant&#8217;s target
      annual bonus under the Company&#8217;s annual cash bonus plan or policy then in effect (and without giving effect to any reduction in target bonus that would give rise to the Participant&#8217;s right to resign for Good Reason or which is implemented following a
      Change in Control); <font style="font-style: italic;">provided that</font>, if the Company does not maintain such a plan or policy, then the last target bonus prior to the Change in Control.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M25"></a><a name="z_Ref296413611"></a><font style="font-weight: bold;">3.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-variant: small-caps;">Eligibility for Benefits.</font><a name="z_DV_M26"></a><font style="font-weight: bold; font-variant: small-caps;">&#160;</font><a name="z_DV_M27"></a>Subject to the terms and conditions of the Plan, the Company will provide the benefits described in Section 5 to the affected Participant. A Participant will not
      receive benefits under the Plan (or will receive reduced benefits under the Plan) in the following circumstances, as determined by the Plan Administrator, in its sole discretion:</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M28"></a><a name="z_DV_M29"></a><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Participant&#8217;s employment is terminated by either the Company or the Participant for any reason
      other than a Qualifying Termination;</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M30"></a><a name="z_Ref308536659"></a><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Participant is rehired by the Company or an Affiliate and recommences employment prior to
      the date benefits under the Plan are scheduled to commence.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; The Participant has not entered into the Company&#8217;s standard form of Employee Invention Assignment and Confidentiality Agreement or any similar or
      successor document (the &#8220;<font style="font-weight: bold; font-style: italic;">Confidentiality Agreement</font>&#8221;);<a name="z_DV_M31"></a></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M32"></a><font style="font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Participant has failed to execute and allow to become effective the Release within the Release Period; and</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M33"></a><font style="font-weight: bold;">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Participant has failed to return all Company Property. For this purpose, &#8220;<font style="font-weight: bold; font-style: italic;">Company Property</font>&#8221; means all paper and electronic Company documents (and all copies thereof) created and/or received by the Participant during his or her period of employment with the Company and other Company materials and property
      that the Participant has in his or her possession or control, including, without limitation, Company files, notes, drawings, records, plans, forecasts, reports, studies, analyses, proposals, agreements, financial information, research and development
      information, sales and marketing information, operational and personnel information, specifications, code, software, databases, computer-recorded information, tangible property and equipment (including, without limitation, leased vehicles, computers,
      computer equipment, software programs, facsimile machines, mobile telephones, servers), credit and calling cards, entry cards, identification badges and keys, and any materials of any kind that contain or embody any proprietary or confidential
      information of the Company (and all reproductions thereof, in whole or in part). As a condition to receiving benefits under the Plan, a Participant must not make or retain copies, reproductions or summaries of any such Company Property. However, a
      Participant is not required to return his or her personal copies of documents evidencing the Participant&#8217;s hire, termination, compensation, benefits and stock options and any other documentation received as a stockholder of the Company.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 4 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify;"><font style="font-weight: bold;">4.</font>&#160;&#160;&#160;&#160;&#160; &#160; &#160;&#160; <font style="font-weight: bold;">No Duplicative Benefits Provided Under Plan.</font>&#160; This Plan does not supersede the terms of any Individual Severance Arrangement
      or Equity Award in effect as of the Effective Date.&#160; Unless otherwise determined by the Plan Administrator in its sole discretion, if a Participant is otherwise eligible to receive severance benefits under this Plan that are of the same category and
      would otherwise duplicate the benefits available under the terms of any Individual Severance Arrangement (&#8220;<font style="font-weight: bold; font-style: italic;">Duplicative Benefits</font>&#8221;), such Participant will receive severance benefits under the
      Individual Severance Arrangement in lieu of any Plan benefits to the extent such benefits are Duplicative Benefits, and severance benefits will be provided under the Plan only to the extent, if any, that Plan benefits are not Duplicative Benefits.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M34"></a><a name="z_DV_M35"></a><a name="z_DV_M36"></a><a name="z_DV_M37"></a><a name="z_DV_M38"></a><a name="z_Ref296431398"></a><a name="z_Ref308600973"></a><a name="z_Ref296419222"></a><font style="font-weight: bold;">5.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-variant: small-caps;">Payments &amp; Benefits Upon a Qualifying Termination</font><font style="font-weight: bold;">. </font>Except as may otherwise be provided in
      the Participant&#8217;s Participation Notice, in the event of a Qualifying Termination, the Company will provide the payments and benefits described in this Section 5, subject to the terms and conditions of the Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M41"></a><a name="z_DV_M42"></a><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Payment of Accrued Obligations. </font>The Company shall pay to
      each eligible Participant who incurs a Qualifying Termination a lump sum payment in cash, paid in accordance with applicable law, equal to<font style="font-weight: bold;">&#160;</font>the sum of (i)<font style="font-weight: bold;">&#160;</font>the
      Participant&#8217;s accrued but unpaid base salary and any accrued but unpaid vacation pay through the date of the Qualifying Termination, and (ii) any earned but unpaid annual bonus for any fiscal year preceding the fiscal year in which the termination
      occurs.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Non-CiC Termination.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Cash Severance</font>. Subject to the execution (and non-revocation) of the Release, upon a Non-CiC Termination,
      the Participant will receive as severance an amount equal to the Participant&#8217;s Non-CiC Severance Base Pay (as defined below), and for the Chief Executive Officer only, the Pro-rated Target Bonus. Such amounts will be payable in accordance with
      Section 5(b)(i)(2) below.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(1)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">Non-CiC Severance Base Pay</font>. For this purpose, &#8220;<font style="font-weight: bold; font-style: italic;">Non-CiC Severance Base Pay</font>&#8221; means an amount equal to the product of (A) the Participant&#8217;s annual base salary or annualized wages (excluding incentive pay, premium pay, commissions, overtime, bonuses and other forms of
      variable compensation) as in effect on the date of the Qualifying Termination and (B) a fraction, the numerator of which is the number of months represented by the Non-CiC Severance Period and the denominator of which is twelve (12).</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 5 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(2)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">Payment Schedule</font>. The Company will pay the Non-CiC Severance Base Pay and, for the
      Chief Executive Officer only, the Pro-rated Target Bonus in a lump sum on the first payroll date that occurs more than five (5) days after the Release Effective Date. Notwithstanding the foregoing, to the extent required to comply with Section 409A
      (as defined below), if the Release Period spans two calendar years such that the Release Effective Date could occur in either of such calendar years, the Non-CiC Severance Base Pay and, if applicable, the Pro-rated Target Bonus to be paid to the
      Participant will be made in the second calendar year.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">COBRA Payments; Special Severance Payments.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(1)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">COBRA Payment Period</font><font style="font-style: italic;">. </font>If the Participant is
      eligible for and has made the necessary elections for continuation coverage pursuant to COBRA under a group health, dental or vision plan sponsored by the Company, the Company will pay, as and when due directly to the COBRA carrier, the premiums
      sufficient to continue the Participant&#8217;s COBRA coverage for the Participant and the Participant&#8217;s eligible dependents from the date of the Non-CIC Termination until the earliest to occur of (i) the end of the Non-CiC Severance Period, (ii) the
      expiration of the Participant&#8217;s eligibility for the continuation coverage under COBRA, and (iii) the date on which the Participant becomes eligible for health insurance coverage in connection with new employment or self-employment (such period, the &#8220;<font style="font-weight: bold; font-style: italic;">Non-CiC COBRA Payment Period</font>&#8221;). The Participant agrees to promptly notify the Company as soon as the Participant becomes eligible for health insurance coverage in connection with new employment
      or self-employment.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><a name="z_Ref296427693"></a><a name="z_Ref296443424"></a><font style="font-weight: bold;">(2)</font>&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">Special Severance Payment</font>.
      Notwithstanding Section 5(b)(ii)(1) above, if at any time the Company determines, in its sole discretion, that the payment of the COBRA premiums would result in a violation of the nondiscrimination rules of Section 105(h)(2) of the Code or any
      statute or regulation of similar effect (including, without limitation, the 2010 Patient Protection and Affordable Care Act, as amended by the 2010 Health Care and Education Reconciliation Act and any other subsequent amendments), then in lieu of
      providing the benefit set forth in Section 5(b)(ii)(1) above, the Company will instead pay the Participant, on the first day of each month of the remainder of the Non-CiC COBRA Payment Period, a fully taxable cash payment equal to the COBRA premiums
      for that month, subject to applicable tax withholdings and deductions (such amount, the &#8220;<font style="font-weight: bold; font-style: italic;">Non-CiC Special Severance Payment</font>&#8221;).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(3)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">Payment Schedule</font><font style="font-weight: bold;">. </font>The Company will make the
      first payment under this Section 5(b)(ii) (and, in the case of the Non-CiC Special Severance Payment, such payment will be made to the Participant, in a lump sum) within five (5) business days after the Release Effective Date. Notwithstanding the
      foregoing, to the extent required to comply with Section 409A (as defined below), if the Release Period spans two calendar years such that the Release Effective Date could occur in either of such calendar years, the first payment to be made under
      this Section 5(b)(ii) will be made in the second calendar year (and, if applicable, will include any amounts that the Company otherwise would have paid through such date), with the balance of the payments (if applicable) paid thereafter on the
      original schedule.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Accelerated Vesting. </font>Subject to the Participant&#8217;s execution (and non-revocation) of the Release, upon a
      Non-CiC Termination, the vesting and exercisability (if applicable) of all outstanding unvested time-based equity awards granted under the Company&#8217;s equity incentive plans that are held by a Participant on the date of the Non-CiC Termination that
      otherwise would have vested with the passage of time over the entirety of the Non-CiC Severance Period had the Participant remained in Continuous Service with the Company will be accelerated.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 6 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M55"></a><a name="z_DV_M58"></a><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Change in Control Termination.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(i)</font>&#160;&#160; &#160;&#160; &#160;&#160; <font style="font-weight: bold;">Cash Severance</font>. Subject to the execution (and non-revocation) of the Release, upon a Change in Control
      Termination, the Participant will receive as severance an amount equal to the Participant&#8217;s CiC Severance Base Pay and Target Bonus Multiple (both as defined below). Such amount will be payable in accordance with Section 5(c)(i)(3) below.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(1)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">CiC Severance Base Pay</font>. For this purpose, &#8220;<font style="font-weight: bold; font-style: italic;">CiC Severance Base Pay</font>&#8221; means an amount equal to the product of (A) the Participant&#8217;s annual base salary or annualized wages (excluding incentive pay, premium pay, commissions, overtime, bonuses and other forms of
      variable compensation) as in effect on the date of the Change in Control and (B) a fraction, the numerator of which is the number of months represented by the CiC Severance Period and the denominator of which is twelve (12).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(2)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">Target Bonus Multiple</font>. For this purpose, &#8220;<font style="font-weight: bold; font-style: italic;">Target Bonus Multiple</font>&#8221; means an amount equal to the product of (A) the Participant&#8217;s Target Bonus as in effect on the date of the Change in Control and (B) a fraction, the numerator of which is the number of months represented by
      the CiC Severance Period and the denominator of which is twelve (12).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(3)</font>&#160; &#160; &#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">Payment Schedule</font>. The Company will pay the CiC Severance Base Pay and Target Bonus
      Multiple in a lump sum on the first payroll date that occurs more than five (5) days after the Release Effective Date. Notwithstanding the foregoing, to the extent required to comply with Section 409A (as defined below), if the Release Period spans
      two calendar years such that the Release Effective Date could occur in either of such calendar years, the CiC Severance Base Pay and Target Bonus Multiple to be paid to the Participant will be made in the second calendar year.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">COBRA Payments; Special Severance Payments.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(1)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-style: italic;">COBRA Payment Period</font><font style="font-style: italic;">. </font>If the Participant is
      eligible for and has made the necessary elections for continuation coverage pursuant to COBRA under a group health, dental or vision plan sponsored by the Company, the Company will pay, as and when due directly to the COBRA carrier, the premiums
      sufficient to continue the Participant&#8217;s COBRA coverage for the Participant and the Participant&#8217;s eligible dependents from the date of the Change in Control Termination until the earliest to occur of (A) the end of the CiC Severance Period, (B) the
      expiration of the Participant&#8217;s eligibility for the continuation coverage under COBRA, and (C) the date on which the Participant becomes eligible for health insurance coverage in connection with new employment or self-employment (such period, the &#8220;<font style="font-weight: bold; font-style: italic;">CiC COBRA Payment Period</font>&#8221;). The Participant agrees to promptly notify the Company as soon as the Participant becomes eligible for health insurance coverage in connection with new employment or
      self-employment.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(2)</font> &#160; &#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">Special Severance Payment</font>. Notwithstanding Section 5(c)(ii)(1) above, if at any time
      the Company determines, in its sole discretion, that the payment of the COBRA premiums would result in a violation of the nondiscrimination rules of Section 105(h)(2) of the Code or any statute or regulation of similar effect (including, without
      limitation, the 2010 Patient Protection and Affordable Care Act, as amended by the 2010 Health Care and Education Reconciliation Act and any other subsequent amendments), then in lieu of providing the benefit set forth in Section 5(c)(ii)(1) above,
      the Company will instead pay the Participant, on the first day of each month of the remainder of the CiC COBRA Payment Period, a fully taxable cash payment equal to the COBRA premiums for that month, subject to applicable tax withholdings and
      deductions (such amount, the &#8220;<font style="font-weight: bold; font-style: italic;">CiC Special Severance Payment</font>&#8221;).</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 7 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 108pt;"><font style="font-weight: bold;">(3)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-style: italic;">Payment Schedule</font><font style="font-weight: bold;">. </font>The Company will make the
      first payment under this Section 5(c)(ii) (and, in the case of the CiC Special Severance Payment, such payment will be made to the Participant, in a lump sum) within five (5) business days after the Release Effective Date. Notwithstanding the
      foregoing, to the extent required to comply with Section 409A (as defined below), in the event that the Release Period spans two calendar years such that the Release Effective Date could occur in either of such calendar years, the first payment to be
      made under this Section 5(c)(ii) will be made in the second calendar year (and, if applicable, will include any amounts that the Company otherwise would have paid through such date), with the balance of the payments (if applicable) paid thereafter on
      the original schedule.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Accelerated Vesting. </font>Subject to the Participant&#8217;s execution (and non-revocation) of the Release, upon a
      Change in Control Termination, the vesting and exercisability (if applicable) of all outstanding unvested time-based equity awards granted under the Company&#8217;s equity incentive plans that are held by a Participant on the date of the Change in Control
      Termination will be accelerated in full.&#160; Notwithstanding the foregoing, if, in connection with a Change in Control, an equity award will terminate and will not be so assumed or continued by the successor or acquiror entity in such Change in Control
      or substituted for a similar award of the successor or acquiror entity, then, the Participant will become vested, with respect to 100 percent of any then unvested portion of any applicable equity award, effective immediately prior to, but subject to
      the consummation of such Change in Control.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><font style="font-weight: bold;">6.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold;"><font style="font-variant: small-caps;">Conditions and Limitations on Benefits</font>.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M59"></a><a name="z_Ref296430717"></a><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Release. </font>To be eligible to receive any benefits under
      the Plan, a Participant must sign a general waiver and release in substantially the form attached hereto as <font style="font-weight: bold; font-variant: small-caps;">Exhibit B</font>, <font style="font-weight: bold; font-variant: small-caps;">Exhibit

        C</font>, or <font style="font-weight: bold; font-variant: small-caps;">Exhibit D</font>, as appropriate (the &#8220;<font style="font-weight: bold; font-style: italic;">Release</font>&#8221;), and such release must be executed (and not revoked) by the
      Participant in accordance with its terms, in each case within the Release Period. The Plan Administrator, in its sole discretion, may modify the form of the required Release to comply with applicable law, and any such Release may be incorporated into
      a termination agreement or other agreement with the Participant.<a name="z_DV_M60"></a></div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 8 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M61"></a><a name="z_Ref296432159"></a><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Prior Agreements; Certain Reductions. </font>The Plan
      Administrator will reduce a Participant&#8217;s benefits under the Plan by any other statutory severance obligations or contractual severance benefits, obligations for pay in lieu of notice, and any other similar benefits payable to the Participant by the
      Company (or any successor thereto) that are due in connection with the Participant&#8217;s Qualifying Termination and that are in the same form as the benefits provided under the Plan (e.g., equity award vesting credit). Without limitation, this reduction
      includes a reduction for any benefits required pursuant to (i) any applicable legal requirement, including, without limitation, the Worker Adjustment and Retraining Notification Act of 1988 and any similar state or local laws (collectively, the &#8220;<font style="font-weight: bold; font-style: italic;">WARN Act</font>&#8221;), (ii) a written employment, severance or equity award agreement with the Company, (iii) any Company policy or practice providing for the Participant to remain on the payroll for a
      limited period of time after being given notice of the termination of the Participant&#8217;s employment, and (iv) any required salary continuation, notice pay, statutory severance payment, or other payments either required by local law, or owed pursuant
      to a collective labor agreement, as a result of the termination of the Participant&#8217;s employment. The benefits provided under the Plan are intended to satisfy, to the greatest extent possible, and not to provide benefits duplicative of, any and all
      statutory, contractual and collective agreement obligations of the Company in respect of the form of benefits provided under the Plan that may arise out of a Qualifying Termination, and the Plan Administrator will so construe and implement the terms
      of the Plan. Reductions may be applied on a retroactive basis, with benefits previously provided being recharacterized as benefits pursuant to the Company&#8217;s statutory or other contractual obligations. The payments pursuant to the Plan are in addition
      to, and not in lieu of, any unpaid salary, bonuses or employee welfare benefits to which a Participant may be entitled for the period ending with the Participant&#8217;s Qualifying Termination.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M63"></a><a name="z_DV_M64"></a><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Indebtedness of Participants. </font>If a Participant is indebted
      to the Company on the effective date of his or her Qualifying Termination, the Company reserves the right to offset the payment of any benefits under the Plan by the amount of such indebtedness. Such offset will be made in accordance with all
      applicable laws. The Participant&#8217;s execution of the Participation Notice constitutes knowing written consent to the foregoing.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M65"></a><font style="font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Parachute Payments; No-Gross Ups.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Except as otherwise expressly provided in an agreement between a Participant and the Company, if any payment or benefit the Participant would
      receive in connection with a Change in Control from the Company or otherwise (a &#8220;<font style="font-weight: bold; font-style: italic;">Payment</font>&#8221;) would (A) constitute a &#8220;parachute payment&#8221; within the meaning of Section 280G of the Code, and (B)
      but for this sentence, be subject to the excise tax imposed by Section 4999 of the Code (the &#8220;<font style="font-weight: bold; font-style: italic;">Excise Tax</font>&#8221;), then such Payment will be equal to the Reduced Amount. The &#8220;<font style="font-weight: bold; font-style: italic;">Reduced Amount</font>&#8221; will be either (1) the largest portion of the Payment that would result in no portion of the Payment being subject to the Excise Tax, or (2) the largest portion, up to and
      including the total, of the Payment, whichever amount ((1) or (2)), after taking into account all applicable federal, state, provincial, foreign, and local employment taxes, income taxes, and the Excise Tax (all computed at the highest applicable
      marginal rate), results in the Participant&#8217;s receipt, on an after-tax basis, of the greatest economic benefit notwithstanding that all or some portion of the Payment may be subject to the Excise Tax. If a reduction in payments or benefits
      constituting &#8220;parachute payments&#8221; is necessary so that the Payment equals the Reduced Amount, reduction in the payments and/or benefits will occur in the manner that results in the greatest economic benefit to the Participant, as determined in this
      paragraph; <font style="font-style: italic;">provided</font>, that if more than one method of reduction will result in the same economic benefit, the portions of the Payment shall be reduced pro rata.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; The professional firm engaged by the Company for general tax purposes as of the day prior to the effective date of the Change in Control shall make
      all determinations required to be made under this Section 6(d). If the professional firm so engaged by the Company is serving as an accountant or auditor for the individual, entity or group effecting the Change in Control, the Company shall appoint a
      nationally recognized independent registered public accounting firm to make the determinations required hereunder. The Company shall bear all expenses with respect to the determinations by such professional firm required to be made hereunder. Any
      good faith determinations of the professional firm made hereunder shall be final, binding and conclusive upon the Company and the Participant.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 9 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-weight: bold;">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Participants are not eligible to receive any tax gross-up payments under this Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M66"></a><a name="z_Ref296428567"></a><font style="font-weight: bold;">7.</font>&#160;&#160;&#160;&#160;&#160; &#160; &#160;&#160; <font style="font-weight: bold;"><font style="font-variant: small-caps;">Tax Matters</font>.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M67"></a><a name="z_Ref296430620"></a><a name="z_Ref296431055"></a><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Application of Section 409A of
        the Code. </font>It is intended that all of the payments and benefits provided under the Plan satisfy, to the greatest extent possible, the exemptions from the application of Section 409A of the Code and the regulations and other guidance
      thereunder and any state law of similar effect (collectively, &#8220;<font style="font-weight: bold; font-style: italic;">Section 409A</font>&#8221;) provided under Treasury Regulations Sections 1.409A-1(b)(4), 1.409A-1(b)(5), and 1.409A-1(b)(9), and the Plan
      will be construed to the greatest extent possible as consistent with those provisions. To the extent not so exempt, the Plan (and any definitions in the Plan) will be construed in a manner that complies with Section 409A, and will incorporate by
      reference all required definitions and payment terms. Notwithstanding anything to the contrary herein, to the extent required to comply with Section 409A, a termination of employment shall not be deemed to have occurred for purposes of any provision
      of the Plan providing for the payments of amounts or benefits upon or following a termination of employment unless such termination is also a &#8220;separation from service&#8221; within the meaning of Section 409A and, for purposes of any such provision of the
      Plan, references to a &#8220;resignation,&#8221; &#8220;termination, &#8220;termination of employment&#8221; or like terms shall mean separation from service. For purposes of Section 409A (including, without limitation, for purposes of Treasury Regulations Section
      1.409A-2(b)(2)(iii)), a Participant&#8217;s right to receive any installment payments under the Plan will be treated as a right to receive a series of separate payments and, accordingly, each installment payment under the Plan will at all times be
      considered a separate and distinct payment. If the Plan Administrator determines that any of the payments upon a Separation from Service provided under the Plan (or under any other arrangement with the Participant) constitute &#8220;deferred compensation&#8221;
      under Section 409A and if the Participant is a &#8220;specified employee&#8221; of the Company, as such term is defined in Section 409A(a)(2)(B)(i), at the time of his or her Separation from Service, then, solely to the extent necessary to avoid the incurrence
      of the adverse personal tax consequences under Section 409A, the timing of the payments upon a Separation from Service will be delayed as follows: on the earlier to occur of (i) the date that is six (6) months and one (1) day after the effective date
      of the Participant&#8217;s Separation from Service, and (ii) the date of the Participant&#8217;s death (such earlier date, the &#8220;<font style="font-weight: bold; font-style: italic;">Delayed Initial Payment Date</font>&#8221;), the Company will (A) pay to the
      Participant a lump sum amount equal to the sum of the payments upon Separation from Service that the Participant would otherwise have received through the Delayed Initial Payment Date if the commencement of the payments had not been delayed pursuant
      to this Section <a name="z_DV_M69"></a>6(a), and (B) commence paying the balance of the payments in accordance with the applicable payment schedules set forth above. No interest will be due on any amounts so deferred<a name="z_DV_M70"></a>.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M71"></a><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Withholding. </font>All payments and benefits under the Plan will be subject to all
      applicable deductions and withholdings, including, without limitation, obligations to withhold for federal, state, provincial, foreign and local income and employment taxes.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 10 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M72"></a><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Tax Advice. </font>By becoming a Participant in the Plan, the Participant agrees to
      review with Participant&#8217;s own tax advisors the federal, state, provincial, local, and foreign tax consequences of participation in the Plan. The Participant will rely solely on such advisors and not on any statements or representations of the Company
      or any of its agents. The Participant understands that the Participant (and not the Company) will be responsible for the Participant&#8217;s own tax liability that may arise as a result of becoming a Participant in the Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M73"></a><font style="font-weight: bold;">8.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Reemployment</font><font style="font-weight: bold;">. </font>In the event of a
      Participant&#8217;s reemployment by the Company or one of its Affiliates during the CiC Severance Period or Non-CiC Severance Period, as applicable, the Company, in its sole and absolute discretion, may require such Participant to repay to the Company all
      or a portion of such severance benefits as a condition of reemployment.<a name="z_DV_C9"></a></div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_C10"></a><font style="font-weight: bold;">9.</font>&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold; font-variant: small-caps;">Clawback; Recovery</font><font style="font-weight: bold;">. </font>All payments
      and severance benefits provided under the Plan will be subject to recoupment in accordance with any clawback policy that the Company is required to adopt pursuant to the listing standards of any national securities exchange or association on which
      the Company&#8217;s securities are listed or as is otherwise required by the Dodd-Frank Wall Street Reform and Consumer Protection Act or other applicable law. In addition, the Board may impose such other clawback, recovery or recoupment provisions as the
      Board determines necessary or appropriate, including but not limited to a reacquisition right in respect of previously acquired shares of common stock of the Company or other cash or property upon the occurrence of a termination of employment for
      Cause.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M74"></a><font style="font-weight: bold;">10.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><font style="font-variant: small-caps;">Right to Interpret Plan; Amendment and Termination</font>.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M75"></a><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Exclusive Discretion. </font>The Plan Administrator (or the Representative, as applicable)
      will have the exclusive discretion and authority to establish rules, forms, and procedures for the administration of the Plan and to construe and interpret the Plan and to decide any and all questions of fact, interpretation, definition, computation
      or administration arising in connection with the operation of the Plan, including, without limitation, the eligibility to participate in the Plan, the amount of benefits paid under the Plan and any adjustments that need to be made in accordance with
      the laws applicable to a Participant. The rules, interpretations, computations and other actions of the Plan Administrator (or the Representative, as applicable) will be binding and conclusive on all persons.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M76"></a><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Amendment or Termination. </font>This Plan and any Participation Notice executed
      hereunder cannot be amended, modified or terminated with respect to a Participant except by a written agreement signed by the Participant and the Company.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M77"></a><font style="font-weight: bold; font-variant: small-caps;">11.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">No Implied Employment Contract. </font>The Plan will not
      be deemed (i) to give any employee or other service provider any right to be retained in the employ or services of the Company, or (ii) to interfere with the right of the Company to discharge any employee or other service provider at any time, with
      or without Cause, which right is hereby reserved.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M78"></a><font style="font-weight: bold; font-variant: small-caps;">12.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-variant: small-caps;">Legal Construction. </font>The Plan will be governed by
      and construed under the laws of the State of California (without regard to principles of conflict of laws), except to the extent preempted by ERISA.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 11 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify;"><a name="z_DV_M79"></a><a name="z_Ref296433202"></a><font style="font-weight: bold; font-variant: small-caps;">13.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><font style="font-variant: small-caps;">Claims,
          Inquiries And Appeals</font>.<a name="z_DV_M80"></a></font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M81"></a><a name="z_Ref296433176"></a><font style="font-weight: bold; font-variant: small-caps;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Applications for Benefits and
        Inquiries. </font>Any application for benefits, inquiries about the Plan or inquiries about present or future rights under the Plan must be submitted to the Plan Administrator in writing by an applicant (or his or her authorized representative).
      The Plan Administrator is set forth in Section 15(d).<a name="z_DV_M83"></a></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M84"></a><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Denial of Claims.</font> If any application for benefits is denied in whole or in part,
      the Plan Administrator must provide the applicant with written or electronic notice of the denial of the application, and of the applicant&#8217;s right to review the denial. Any electronic notice will comply with the regulations of the U.S. Department of
      Labor. The notice of denial will be set forth in a manner designed to be understood by the applicant and will include the following:</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><a name="z_DV_M85"></a><font style="font-weight: bold;">(1)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;the specific reason or reasons for the denial;</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><a name="z_DV_M86"></a><font style="font-weight: bold;">(2)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;references to the specific Plan provision(s) upon which the denial is based;</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><a name="z_DV_M87"></a><font style="font-weight: bold;">(3)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; a description of any additional information or material that the Plan Administrator needs to complete the review and an
      explanation of why such information or material is necessary; and</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><a name="z_DV_M88"></a><font style="font-weight: bold;">(4)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; an explanation of the Plan&#8217;s review procedures and the time limits applicable to such procedures, including a statement of
      the applicant&#8217;s right to bring a civil action under Section 502(a) of ERISA following a denial on review of the claim, as described in Section <a name="z_DV_M89"></a>13(d).</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M90"></a>The notice of denial will be given to the applicant within ninety (90) days after the Plan Administrator receives the application, unless special circumstances require an extension of time, in
      which case, the Plan Administrator has up to an additional ninety (90) days for processing the application. If an extension of time for processing is required, written notice of the extension will be furnished to the applicant before the end of the
      initial ninety (90) day period.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M91"></a>The notice of extension will describe the special circumstances necessitating the additional time and the date by which the Plan Administrator is to render its decision on the application.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M92"></a><a name="z_Ref296433190"></a><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Request for a Review. </font>Any person (or that person&#8217;s
      authorized representative) for whom an application for benefits is denied, in whole or in part, may appeal the denial by submitting a request for a review to the Plan Administrator within sixty (60) days after the application is denied. A request for
      a review will be in writing and will be addressed to:</div>
    <div>&#160;</div>
    <div style="text-align: center;"><a name="z_DV_M93"></a>Ionis Pharmaceuticals, Inc.<a name="z_DV_M94"></a></div>
    <div style="text-align: center;">Attn: Plan Administrator of the Severance Benefit Plan</div>
    <div style="text-align: center;">2855 Gazelle</div>
    <div style="text-align: center;">Carlsbad, California 92010</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 12 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify;"><a name="z_DV_M97"></a>A request for review must set forth all of the grounds on which it is based, all facts in support of the request and any other matters that the applicant feels are pertinent. The applicant (or
      the applicant&#8217;s representative) will have the opportunity to submit (or the Plan Administrator may require the applicant to submit) written comments, documents, records, and other information relating to his or her claim. The applicant (or his or her
      representative) will be provided, upon request and free of charge, reasonable access to, and copies of, all documents, records and other information relevant to his or her claim. The review will take into account all comments, documents, records and
      other information submitted by the applicant (or his or her representative) relating to the claim, without regard to whether such information was submitted or considered in the initial benefit determination.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M98"></a><a name="z_Ref296443614"></a><font style="font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Decision on Review. </font>The Plan Administrator will act
      on each request for review within sixty (60) days after receipt of the request, unless special circumstances require an extension of time (not to exceed an additional sixty (60) days), for processing the request for a review. If an extension for
      review is required, written notice of the extension will be furnished to the applicant within the initial sixty (60) day period. This notice of extension will describe the special circumstances necessitating the additional time and the date by which
      the Plan Administrator is to render its decision on the review. The Plan Administrator will give prompt, written or electronic notice of its decision to the applicant. Any electronic notice will comply with the regulations of the U.S. Department of
      Labor. If the Plan Administrator confirms the denial of the application for benefits, in whole or in part, the notice will set forth, in a manner designed to be understood by the applicant, the following:</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><a name="z_DV_M99"></a><font style="font-weight: bold;">(1)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;the specific reason or reasons for the denial;</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><a name="z_DV_M100"></a><font style="font-weight: bold;">(2)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;references to the specific Plan provision(s) upon which the denial is based;</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><a name="z_DV_M101"></a><font style="font-weight: bold;">(3)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; a statement that the applicant is entitled to receive, upon request and free of charge, reasonable access to, and copies
      of, all documents, records and other information relevant to the applicant&#8217;s claim; and</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 108pt;"><a name="z_DV_M102"></a><font style="font-weight: bold;">(4)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; a statement of the applicant&#8217;s right to bring a civil action under Section 502(a) of ERISA.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M103"></a><font style="font-weight: bold;">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Rules and Procedures. </font>The Plan Administrator will establish rules and procedures,
      consistent with the Plan and with ERISA, as necessary and appropriate in carrying out its responsibilities in reviewing benefit claims. The Plan Administrator may require an applicant who wishes to submit additional information in connection with an
      appeal from the denial of benefits to do so at the applicant&#8217;s own expense.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M104"></a><font style="font-weight: bold;">(f)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Exhaustion of Remedies. </font>No legal action for benefits under the Plan may be brought
      until the applicant (i) has submitted a written application for benefits in accordance with the procedures described by Section <a name="z_DV_M105"></a>13(a), (ii) has been notified by the Plan Administrator that the application is denied, (iii) has
      filed a written request for a review of the application in accordance with the appeal procedure described in Section <a name="z_DV_C22"></a>13<a name="z_DV_M106"></a>(c), and (iv) has been notified that the Plan Administrator has denied the appeal.
      Notwithstanding the foregoing, if the Plan Administrator does not respond to an applicant&#8217;s claim or appeal within the relevant time limits specified in this Section <a name="z_DV_C24"></a>13,<a name="z_DV_M107"></a> the applicant may bring legal
      action for benefits under the Plan pursuant to Section 502(a) of ERISA.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 13 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify;"><a name="z_DV_M108"></a><font style="font-weight: bold;">14.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold; font-variant: small-caps;">Basis Of Payments To And From Plan</font><font style="font-weight: bold;">. </font>All

      benefits under the Plan will be paid by the Company. The Plan will be unfunded, and benefits hereunder will be paid only from the general assets of the Company.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M109"></a><font style="font-weight: bold;">15.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><font style="font-variant: small-caps;">Other Plan Information</font>.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M110"></a><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Employer and Plan Identification Numbers.</font> The Employer Identification Number
      assigned to the Company (which is the &#8220;Plan Sponsor&#8221; as that term is used in ERISA) by the Internal Revenue Service is 33-0336973. The Plan Number assigned to the Plan by the Plan Sponsor pursuant to the instructions of the Internal Revenue Service
      is 511.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M111"></a><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Ending Date for Plan&#8217;s Fiscal Year. </font>The date of the end of the fiscal year for
      the purpose of maintaining the Plan&#8217;s records is December 31.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M112"></a><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Agent for the Service of Legal Process</font>. The agent for the service of legal process
      with respect to the Plan is:</div>
    <div>&#160;</div>
    <div style="text-align: center;"><a name="z_DV_M113"></a>Ionis Pharmaceuticals, Inc.<a name="z_DV_M114"></a></div>
    <div style="text-align: center;">Attn: General Counsel</div>
    <div style="text-align: center;">2855 Gazelle</div>
    <div style="text-align: center;">Carlsbad, California 92010</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M117"></a><a name="z_Ref296433901"></a><font style="font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Plan Sponsor and Administrator. </font>The &#8220;Plan Sponsor&#8221;
      and the &#8220;Plan Administrator&#8221; of the Plan is:</div>
    <div>&#160;</div>
    <div style="text-align: center;"><a name="z_DV_M118"></a>Ionis Pharmaceuticals, Inc.<a name="z_DV_M119"></a></div>
    <div style="text-align: center;">Attn: Plan Administrator of the Severance Benefit Plan<a name="z_DV_M120"></a><a name="z_DV_M122"></a></div>
    <div style="text-align: center;">2855 Gazelle</div>
    <div style="text-align: center;">Carlsbad, California 92010</div>
    <div>&#160;</div>
    <div style="text-align: justify;">The Plan Sponsor&#8217;s and Plan Administrator&#8217;s telephone number is (760) 603-3848. The Plan Administrator is the named fiduciary charged with the responsibility for administering the Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M123"></a><a name="z_Ref296433660"></a><font style="font-weight: bold;">16.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><font style="font-variant: small-caps;">Statement Of ERISA Rights</font>.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M124"></a>Participants in the Plan (which is a welfare benefit plan sponsored by Ionis Pharmaceuticals, Inc.) are entitled to certain rights and protections under ERISA. For purposes of
      this Section <a name="z_DV_M125"></a>16 and, under ERISA, Participants are entitled to:</div>
    <div><br>
    </div>
    <div style="text-align: justify; font-weight: bold;"><a name="z_DV_M126"></a>Receive Information About the Plan and Benefits</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M127"></a><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Examine, without charge, at the Plan Administrator&#8217;s office and at other specified locations, such worksites, all
      documents governing the Plan and a copy of the latest annual report (Form 5500 Series), if applicable, filed by the Plan with the U.S. Department of Labor and available at the Public Disclosure Room of the Employee Benefits Security Administration;</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 14 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M128"></a><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Obtain, upon written request to the Plan Administrator, copies of documents governing the operation of the Plan and copies
      of the latest annual report (Form 5500 Series), if applicable, and an updated (as necessary) Summary Plan Description. The Plan Administrator may make a reasonable charge for the copies; and</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M129"></a><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Receive a summary of the Plan&#8217;s annual financial report, if applicable. The Plan Administrator is required by law to
      furnish each Participant with a copy of this summary annual report.</div>
    <div>&#160;</div>
    <div style="text-align: justify; font-weight: bold;"><a name="z_DV_M130"></a>Prudent Actions by Plan Fiduciaries</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M131"></a>In addition to creating rights for Participants, ERISA imposes duties upon the people who are responsible for the operation of the employee benefit plan. The people who operate the Plan, called
      &#8220;fiduciaries&#8221; of the Plan, have a duty to do so prudently and in the interest of Participants and beneficiaries. No one, including a Participant&#8217;s employer, union (if applicable) or any other person, may fire a Participant or otherwise discriminate
      against a Participant in any way to prevent the Participant from obtaining a Plan benefit or exercising a Participant&#8217;s rights under ERISA.</div>
    <div>&#160;</div>
    <div style="text-align: justify; font-weight: bold;"><a name="z_DV_M132"></a>Enforcement of Participant Rights</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M133"></a>If a claim for a Plan benefit is denied or ignored, in whole or in part, a Participant has a right to know why this was done, to obtain copies of documents relating to the decision without
      charge, and to appeal any denial, all within certain time schedules.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M134"></a>Under ERISA, there are steps a Participant can take to enforce the above rights. For instance, if a Participant requests a copy of Plan documents or the latest annual report from the Plan, if
      applicable, and does not receive them within thirty (30) days, the Participant may file suit in a federal court. In such a case, the court may require the Plan Administrator to provide the materials and pay the Participant up to $110 a day until the
      Participant receives the materials, unless the materials were not sent because of reasons beyond the control of the Plan Administrator.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M135"></a>If a Participant has a claim for benefits that is denied or ignored, in whole or in part, the Participant may file suit in a state or federal court.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M136"></a>If a Participant is discriminated against for asserting the Participant&#8217;s rights, the Participant may seek assistance from the U.S. Department of Labor, or may file suit in a federal court. The
      court will decide who should pay court costs and legal fees. If a Participant is successful, the court may order the person the Participant has sued to pay these costs and fees. If the Participant loses, the court may order the Participant to pay
      these costs and fees, for example, if it finds the Participant&#8217;s claim is frivolous.<a name="z_DV_M137"></a></div>
    <div>&#160;</div>
    <div style="text-align: justify; font-weight: bold;">Assistance with Questions</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M138"></a>If a Participant has any questions about the Plan, the Participant should contact the Plan Administrator. If a Participant has any questions about this statement or about the Participant&#8217;s
      rights under ERISA, or if the Participant needs assistance in obtaining documents from the Plan Administrator, the Participant should contact the nearest office of the Employee Benefits Security Administration, U.S. Department of Labor, listed in the
      Participant&#8217;s telephone directory or the Division of Technical Assistance and Inquiries, Employee Benefits Security Administration, U.S. Department of Labor, 200 Constitution Avenue N.W., Washington, D.C. 20210. The Participant may also obtain
      certain publications about the Participant&#8217;s rights and responsibilities under ERISA by calling the publications hotline of the Employee Benefits Security Administration.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">- 15 -</font></div>
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify;"><a name="z_DV_M139"></a><font style="font-weight: bold;">17.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><font style="font-variant: small-caps;">General Provisions</font>.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M140"></a><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Notices. </font>Any notice, demand or request required or permitted to be given by
      either the Company or a Participant pursuant to the terms of the Plan will be in writing and will be deemed given when delivered personally, when received electronically (including email addressed to the Participant&#8217;s Company email account and to the
      Company email account of the Company&#8217;s head of legal affairs), or deposited in the U.S. Mail, First Class with postage prepaid, and addressed to the parties, in the case of the Company, at the address set forth in Section <a name="z_DV_M141"></a>15(d),

      in the case of a Participant, at the address as set forth in the Company&#8217;s employment file maintained for the Participant as previously furnished by the Participant or such other address as a party may request by notifying the other in writing.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M142"></a><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Transfer and Assignment. </font>The rights and obligations of a Participant under the
      Plan may not be transferred or assigned without the prior written consent of the Company. The Plan will be binding upon any surviving entity resulting from a Change in Control and upon any other person who is a successor by merger, acquisition,
      consolidation or otherwise to the business formerly carried on by the Company without regard to whether or not such person or entity actively assumes the obligations hereunder.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M143"></a><font style="font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Waiver. </font>Any party&#8217;s failure to enforce any provision or provisions of the Plan
      will not in any way be construed as a waiver of any such provision or provisions, nor prevent any party from thereafter enforcing each and every other provision of the Plan. The rights granted to the parties herein are cumulative and will not
      constitute a waiver of any party&#8217;s right to assert all other legal remedies available to it under the circumstances.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M144"></a><font style="font-weight: bold;">(d)</font>&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold;">Severability. </font>Should any provision of the Plan be declared or determined to be
      invalid, illegal or unenforceable, the validity, legality and enforceability of the remaining provisions will not in any way be affected or impaired.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M145"></a><font style="font-weight: bold;">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Section Headings. </font>Section headings in the Plan are included only for convenience
      of reference and will not be considered part of the Plan for any other purpose.</div>
    <div>&#160;</div>
    <div style="text-align: justify;"><a name="z_DV_M146"></a><font style="font-weight: bold;">18.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Effective Date</font><font style="font-weight: bold;">. </font>The Plan shall
      become effective on the Effective Date.</div>
    <div>&#160;</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">- 16 -</font></div>
      <div id="DSPFPageBreak" style="page-break-after:always;">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Exhibit A</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Amended and Restated</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Severance Benefit Plan</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Participation Notice</div>
    <div>&#160;</div>
    <div>To:___________________</div>
    <div>&#160;</div>
    <div>Date:_________________</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">Ionis Pharmaceuticals, Inc. (the &#8220;<font style="font-weight: bold; font-style: italic;">Company</font>&#8221;) has adopted the Amended and Restated Ionis Pharmaceuticals, Inc. Severance Benefit Plan (the &#8220;<font style="font-weight: bold; font-style: italic;">Plan</font>&#8221;). The Company is providing you this Participation Notice to inform you that you have been designated as a Participant in the Plan. A copy of the Plan document is attached to this
      Participation Notice. The terms and conditions of your participation in the Plan are as set forth in the Plan and this Participation Notice, which together constitute the Summary Plan Description for the Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">Your Non-CiC Severance Period is <font style="font-weight: bold;">[XX months]</font><sup style="font-weight: bold; vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup><font style="font-weight: bold;">.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">Your CiC Severance Period is<font style="font-weight: bold;"> [XX months]</font><sup style="font-weight: bold; vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup><font style="font-weight: bold;">.</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">Please return to the Company&#8217;s head of Human Resources a copy of this Participation Notice signed by you and retain a copy of this Participation Notice, along with the Plan document, for your
      records.</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" border="0" id="z06e8c44b75bb401da5990a118568a3e3" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td style="width: 50%; vertical-align: top;">
            <div style="font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div style="text-align: center; font-style: italic;">(Signature)</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div>Name:</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div>Title:</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div style="font-variant: small-caps; font-weight: bold;">Participant:</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div style="text-align: center; font-style: italic;">(Signature)</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
          </td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div>Name:</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
          </td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div>Date:</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>

    </table>
    <br>
    <hr noshade="noshade" align="left" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto 0px 0px; height: 2px; width: 20%; color: #000000;">
    <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;"><br>
        1</sup> 18 months for CEO, 12 months for EVPs, 9 months for SVPs, and 6 months for VPs.</div>
    <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup> 24 months for CEO, 18 months for EVPs, 12 months for SVPs, and 9 months for VPs.</div>
    <div> <br>
    </div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageBreak" style="page-break-after:always;">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Exhibit B</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><a name="z_DV_M163"></a>Release Agreement</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">[Employees Age 40 or Over; Individual Termination]</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-weight: bold;"><a name="z_DV_M164"></a>I understand and agree completely to the terms set forth in the Amended and Restated Ionis Pharmaceuticals, Inc. Severance Benefit Plan (the &#8220;<font style="font-style: italic;">Plan</font>&#8221;).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M165"></a>I understand that this Release, together with the Plan, constitutes the complete, final and exclusive embodiment of the entire agreement between the Company, affiliates of the
      Company and me with regard to the subject matter hereof. I am not relying on any promise or representation by the Company or an affiliate of the Company that is not expressly stated therein. Certain capitalized terms used in this Release are defined
      in the Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M166"></a>I hereby confirm my obligations under my Confidentiality Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">I hereby resign all positions (if any) I hold on the Company&#8217;s Board of Directors, including all committees.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M167"></a>Except as otherwise set forth in this Release, I hereby generally and completely release the Company and its affiliates, and their parents, subsidiaries, successors,
      predecessors and affiliates, and its and their partners, members, directors, officers, employees, stockholders, shareholders, agents, attorneys, predecessors, insurers, affiliates and assigns, from any and all claims, liabilities and obligations,
      both known and unknown, that arise out of or are in any way related to events, acts, conduct, or omissions occurring at any time prior to and including the date I sign this Release. This general release includes, but is not limited to: (a) all claims
      arising out of or in any way related to my employment with the Company and its affiliates, or their affiliates, or the termination of that employment; (b) all claims related to my compensation or benefits, including salary, bonuses, commissions,
      vacation pay, expense reimbursements, severance pay, fringe benefits, stock, stock options, or any other ownership interests in the Company and its affiliates, or their affiliates; (c) all claims for breach of contract, wrongful termination, and
      breach of the implied covenant of good faith and fair dealing; (d) all tort claims, including claims for fraud, defamation, emotional distress, and discharge in violation of public policy; and (e) all federal, state, provincial and local statutory
      claims, including claims for discrimination, harassment, retaliation, attorneys&#8217; fees, or other claims arising under [the Massachusetts Payment of Wages Law (Mass. Gen. Laws ch. 149 &#167; 148),]<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">3</sup> the federal Civil Rights Act of 1964 (as amended), the federal Americans with Disabilities Act of 1990 (as amended), the federal Age Discrimination in Employment Act (as amended) (&#8220;<font style="font-weight: bold; font-style: italic;">ADEA</font>&#8221;), and the federal Employee Retirement Income Security Act of 1974 (as amended).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M168"></a>Notwithstanding the foregoing, I understand that the following rights or claims are not included in my Release: (a) any rights or claims for indemnification I may have
      pursuant to any written indemnification agreement with the Company or its affiliate to which I am a party; the charter, bylaws, or operating agreements of the Company or its affiliate; or under applicable law; or (b) any rights which cannot be waived
      as a matter of law. In addition, I understand that nothing in this Release prevents me from filing, cooperating with, or participating in any proceeding before the Equal Employment Opportunity Commission or the Department of Labor, except that I
      hereby waive my right to any monetary benefits in connection with any such claim, charge or proceeding. I hereby represent and warrant that, other than the claims identified in this paragraph, I am not aware of any claims I have or might have that
      are not included in the Release.</div>
    <div>&#160;</div>
    <div>
      <hr noshade="noshade" align="left" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto 0px 0px; height: 2px; width: 20%; color: #000000;"></div>
    <div>
      <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;"> <br>
        </sup></div>
      <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">3</sup> For Massachusetts employees.</div>
      <div> <br>
      </div>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M169"></a>I acknowledge that I am knowingly and voluntarily waiving and releasing any rights I may have under the ADEA, and that the consideration given under the Plan for the waiver
      and release in the preceding paragraph hereof is in addition to anything of value to which I was already entitled. I further acknowledge that I have been advised by this writing, as required by the ADEA, that: (a) my waiver and release do not apply
      to any rights or claims that may arise after the date I sign this Release; (b) I should consult with an attorney prior to signing this Release (although I may choose voluntarily not to do so); (c) I have twenty-one (21) days to consider this Release
      (although I may choose voluntarily to sign this Release earlier); (d) I have seven (7) days following the date I sign this Release to revoke the Release by providing written notice to an officer of the Company; and (e) this Release will not be
      effective until the date upon which the revocation period has expired, which will be the eighth day after I sign this Release.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M170"></a>I hereby represent that I have been paid all compensation owed and for all hours worked; I have received all the leave and leave benefits and protections for which I am
      eligible pursuant to the Family and Medical Leave Act, or otherwise; and I have not suffered any on-the-job injury for which I have not already filed a workers&#8217; compensation claim.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">I represent that I am not aware of any claim by me other than the claims that are released by this Release. I acknowledge that I may hereafter discover claims or facts in addition to or different
      than those which I now know or believe to exist with respect to the subject matter of this Release and which, if known or suspected at the time of entering into this Release, may have materially affected this Release and my decision to enter into it.
      Nevertheless, I hereby waive any right, claim or cause of action that might arise as a result of such different or additional claims or facts and I hereby expressly waive any and all rights and benefits confirmed upon me by the provisions of
      California Civil Code Section 1542, which provides as set forth below, as well as under any other statute or common law principles of similar effect:</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS THAT THE CREDITOR OR RELEASING PARTY DOES NOT KNOW OR SUSPECT TO EXIST IN HIS OR HER FAVOR AT THE TIME OF EXECUTING THE RELEASE AND THAT, IF KNOWN BY HIM
      OR HER, WOULD HAVE MATERIALLY AFFECTED HIS OR HER SETTLEMENT WITH THE DEBTOR OR RELEASED PARTY.&#8221;]<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">4</sup></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">I agree not to disparage the Company and its affiliates,&#160; and the Company&#8217;s and its affiliates&#8217; officers, directors, employees, shareholders, investors and agents, in any manner likely to be harmful
      to them or their business, business reputation or personal reputation; provided that I may respond accurately and fully to any question, inquiry or request for information when required by legal process or as part of a government investigation.&#160;
      Notwithstanding the foregoing, nothing in this Release shall limit my right to voluntarily communicate with the Equal Employment Opportunity Commission, United States Department of Labor, the National Labor Relations Board, the Securities and
      Exchange Commission, other federal government agency or similar state or local agency or to discuss the terms and conditions of my employment with others to the extent expressly permitted by Section 7 of the National Labor Relations Act.</div>
    <div style="text-align: justify; text-indent: 36pt;"> <br>
    </div>
    <div> <br>
    </div>
    <div>
      <hr noshade="noshade" align="left" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto 0px 0px; height: 2px; width: 20%; color: #000000;"></div>
    <div> <br>
    </div>
    <div>
      <div>
        <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">4</sup> For California employees.</div>
        <div> <br>
        </div>
      </div>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;">I agree that for the one (1) year period after the date my employment ends, I will not, as an officer, director, employee, consultant, owner, partner, or in any other capacity, either directly or
      through others, solicit, induce, encourage, or participate in soliciting, inducing or encouraging any employee, consultant, or independent contractor of Company to terminate his, her or its relationship with Company or its Affiliates, even if I did
      not initiate the discussion or seek out the contact.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M171"></a>I acknowledge that to become effective, I must sign and return this Release to the Company so that it is received not later than twenty-one (21) days following the date it is
      provided to me.</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf7369fba012e41f5b1da270cceeec18b" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td style="width: 50%; vertical-align: top;">
            <div style="font-variant: small-caps; font-weight: bold;">Participant:</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div style="text-align: center; font-style: italic;">(Signature)</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
          </td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div>Name:</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1"><br>
          </td>
          <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1"><br>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
          </td>
          <td style="width: 50%; vertical-align: top;" rowspan="1">
            <div>Date:</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1"><br>
          </td>
          <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1"><br>
          </td>
        </tr>

    </table>
    <div> <br>
    </div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageBreak" style="page-break-after:always;">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><a name="z_DV_M172"></a>Exhibit C</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><a name="z_DV_M173"></a>Release Agreement</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">[Employees Age 40 or Over; Group Termination]</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-weight: bold;"><a name="z_DV_M174"></a>I understand and agree completely to the terms set forth in the Amended and Restated Ionis Pharmaceuticals, Inc. Severance Benefit Plan (the &#8220;<font style="font-style: italic;">Plan</font>&#8221;).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M175"></a>I understand that this Release, together with the Plan, constitutes the complete, final and exclusive embodiment of the entire agreement between the Company, affiliates of the
      Company and me with regard to the subject matter hereof. I am not relying on any promise or representation by the Company or an affiliate of the Company that is not expressly stated therein. Certain capitalized terms used in this Release are defined
      in the Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">I hereby confirm my obligations under my Confidentiality Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">I hereby resign all positions (if any) I hold on the Company&#8217;s Board of Directors, including all committees.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">Except as otherwise set forth in this Release, I hereby generally and completely release the Company and its affiliates, and their parents, subsidiaries, successors, predecessors and affiliates, and
      its and their partners, members, directors, officers, employees, stockholders, shareholders, agents, attorneys, predecessors, insurers, affiliates and assigns, from any and all claims, liabilities and obligations, both known and unknown, that arise
      out of or are in any way related to events, acts, conduct, or omissions occurring at any time prior to and including the date I sign this Release. This general release includes, but is not limited to: (a) all claims arising out of or in any way
      related to my employment with the Company and its affiliates, or their affiliates, or the termination of that employment; (b) all claims related to my compensation or benefits, including salary, bonuses, commissions, vacation pay, expense
      reimbursements, severance pay, fringe benefits, stock, stock options, or any other ownership interests in the Company and its affiliates, or their affiliates; (c) all claims for breach of contract, wrongful termination, and breach of the implied
      covenant of good faith and fair dealing; (d) all tort claims, including claims for fraud, defamation, emotional distress, and discharge in violation of public policy; and (e) all federal, state, provincial and local statutory claims, including claims
      for discrimination, harassment, retaliation, attorneys&#8217; fees, or other claims arising under the [the Massachusetts Payment of Wages Law (Mass. Gen. Laws ch. 149 &#167; 148),]<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">5</sup>
      federal Civil Rights Act of 1964 (as amended), the federal Americans with Disabilities Act of 1990 (as amended), the federal Age Discrimination in Employment Act (as amended) (&#8220;<font style="font-weight: bold; font-style: italic;">ADEA</font>&#8221;), and
      the federal Employee Retirement Income Security Act of 1974 (as amended).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M178"></a>Notwithstanding the foregoing, I understand that the following rights or claims are not included in my Release: (a) any rights or claims for indemnification I may have
      pursuant to any written indemnification agreement with the Company or its affiliate to which I am a party; the charter, bylaws, or operating agreements of the Company or its affiliate; or under applicable law; or (b) any rights which cannot be waived
      as a matter of law. In addition, I understand that nothing in this Release prevents me from filing, cooperating with, or participating in any proceeding before the Equal Employment Opportunity Commission, or the Department of Labor, except that I
      hereby waive my right to any monetary benefits in connection with any such claim, charge or proceeding. I hereby represent and warrant that, other than the claims identified in this paragraph, I am not aware of any claims I have or might have that
      are not included in the Release.</div>
    <div>&#160;</div>
    <div>
      <hr noshade="noshade" align="left" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto 0px 0px; height: 2px; width: 20%; color: #000000;"></div>
    <div> <br>
    </div>
    <div>
      <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">5</sup> For Massachusetts employees.</div>
      <div> <br>
      </div>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M179"></a>I acknowledge that I am knowingly and voluntarily waiving and releasing any rights I may have under the ADEA, and that the consideration given under the Plan for the waiver
      and release in the preceding paragraph hereof is in addition to anything of value to which I was already entitled. I further acknowledge that I have been advised by this writing, as required by the ADEA, that: (a) my waiver and release do not apply
      to any rights or claims that may arise after the date I sign this Release; (b) I should consult with an attorney prior to signing this Release (although I may choose voluntarily not to do so); (c) I have forty-five (45) days to consider this Release
      (although I may choose voluntarily to sign this Release earlier); (d) I have seven (7) days following the date I sign this Release to revoke the Release by providing written notice to an officer of the Company; (e) this Release will not be effective
      until the date upon which the revocation period has expired, which will be the eighth day after I sign this Release; and (f) I have received with this Release a detailed list of the job titles and ages of all employees who were terminated in this
      group termination and the ages of all employees of the Company in the same job classification or organizational unit who were not terminated.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M180"></a>I hereby represent that I have been paid all compensation owed and for all hours worked; I have received all the leave and leave benefits and protections for which I am
      eligible pursuant to the Family and Medical Leave Act, or otherwise; and I have not suffered any on-the-job injury for which I have not already filed a workers&#8217; compensation claim.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">[</font><font style="font-size: 10pt;">I represent that I am not aware of any claim by me other than the claims that are released by
        this Release. I acknowledge that I may hereafter discover claims or facts in addition to or different than those which I now know or believe to exist with respect to the subject matter of this Release and which, if known or suspected at the time of
        entering into this Release, may have materially affected this Release and my decision to enter into it. Nevertheless, I hereby waive any right, claim or cause of action that might arise as a result of such different or additional claims or facts
        and I hereby expressly waive any and all rights and benefits confirmed upon me by the provisions of California Civil Code Section 1542, which provides as set forth below, as well as under any other statute or common law principles of similar
        effect:</font></div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS THAT THE CREDITOR OR RELEASING PARTY DOES NOT KNOW OR SUSPECT TO EXIST IN HIS OR HER FAVOR AT THE TIME OF EXECUTING THE RELEASE AND THAT, IF KNOWN BY HIM
      OR HER, WOULD HAVE MATERIALLY AFFECTED HIS OR HER SETTLEMENT WITH THE DEBTOR OR RELEASED PARTY.&#8221;<font style="font-weight: bold;">]</font><sup style="font-weight: bold; vertical-align: text-top; line-height: 1; font-size: smaller;">6</sup></div>
    <div>&#160;<br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;">I agree not to disparage the Company and its affiliates,&#160; and the Company&#8217;s and its affiliates&#8217; officers, directors, employees, shareholders, investors and agents, in any manner likely to be harmful
      to them or their business, business reputation or personal reputation; provided that I may respond accurately and fully to any question, inquiry or request for information when required by legal process or as part of a government investigation.&#160;
      Notwithstanding the foregoing, nothing in this Release shall limit my right to voluntarily communicate with the Equal Employment Opportunity Commission, United States Department of Labor, the National Labor Relations Board, the Securities and
      Exchange Commission, other federal government agency or similar state or local agency or to discuss the terms and conditions of my employment with others to the extent expressly permitted by Section 7 of the National Labor Relations Act.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">I agree that for the one (1) year period after the date my employment ends, I will not, as an officer, director, employee, consultant, owner, partner, or in any other capacity, either directly or
      through others, solicit, induce, encourage, or participate in soliciting, inducing or encouraging any employee, consultant, or independent contractor of Company to terminate his, her or its relationship with Company or its Affiliates, even if I did
      not initiate the discussion or seek out the contact.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M181"></a>I acknowledge that to become effective, I must sign and return this Release to the Company so that it is received not later than forty-five (45) days following the date it is
      provided to me.</div>
    <div>&#160;</div>
    <div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

          <tr>
            <td style="width: 50%; vertical-align: top;">&#160;</td>
            <td style="width: 50%; vertical-align: top;">
              <div style="font-variant: small-caps; font-weight: bold;">Participant:</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
            <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
            <td style="width: 50%; vertical-align: top;" rowspan="1">
              <div style="text-align: center; font-style: italic;">(Signature)</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
            </td>
            <td style="width: 50%; vertical-align: top;" rowspan="1">
              <div>Name:</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1"><br>
            </td>
            <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1"><br>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
            <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
            </td>
            <td style="width: 50%; vertical-align: top;" rowspan="1">
              <div>Date:</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1"><br>
            </td>
            <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1"><br>
            </td>
          </tr>

      </table>
    </div>
    <div> <br>
    </div>
    <div>
      <div>
        <hr noshade="noshade" align="left" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto 0px 0px; height: 2px; width: 20%; color: #000000;"></div>
      <div>
        <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;"> <br>
          </sup></div>
        <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">6</sup> For California employees.</div>
        <div> <br>
        </div>
      </div>
    </div>
    <div style="text-align: center;"><a name="z_DV_M182"></a></div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageBreak" style="page-break-after:always;">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Exhibit D</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><a name="z_DV_M183"></a>Release Agreement</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">[Employees Under Age 40]</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-weight: bold;"><a name="z_DV_M184"></a>I understand and agree completely to the terms set forth in the Amended and Restated Ionis Pharmaceuticals, Inc. Severance Benefit Plan (the &#8220;<font style="font-style: italic;">Plan</font>&#8221;).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M185"></a>I understand that this Release, together with the Plan, constitutes the complete, final and exclusive embodiment of the entire agreement between the Company, affiliates of the
      Company and me with regard to the subject matter hereof. I am not relying on any promise or representation by the Company or an affiliate of the Company that is not expressly stated therein. Certain capitalized terms used in this Release are defined
      in the Plan.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">I hereby confirm my obligations under my Confidentiality Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">I hereby resign all positions (if any) I hold on the Company&#8217;s Board of Directors, including all committees.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">Except as otherwise set forth in this Release, I hereby generally and completely release the Company and its affiliates, and their parents, subsidiaries, successors, predecessors and affiliates, and
      its and their partners, members, directors, officers, employees, stockholders, shareholders, agents, attorneys, predecessors, insurers, affiliates and assigns, from any and all claims, liabilities and obligations, both known and unknown, that arise
      out of or are in any way related to events, acts, conduct, or omissions occurring at any time prior to and including the date I sign this Release. This general release includes, but is not limited to: (a) all claims arising out of or in any way
      related to my employment with the Company and its affiliates, or their affiliates, or the termination of that employment; (b) all claims related to my compensation or benefits, including salary, bonuses, commissions, vacation pay, expense
      reimbursements, severance pay, fringe benefits, stock, stock options, or any other ownership interests in the Company and its affiliates, or their affiliates; (c) all claims for breach of contract, wrongful termination, and breach of the implied
      covenant of good faith and fair dealing; (d) all tort claims, including claims for fraud, defamation, emotional distress, and discharge in violation of public policy; and (e) all federal, state, provincial and local statutory claims, including claims
      for discrimination, harassment, retaliation, attorneys&#8217; fees, or other claims arising under the [the Massachusetts Payment of Wages Law (Mass. Gen. Laws ch. 149 &#167; 148),]<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">7</sup>
      federal Civil Rights Act of 1964 (as amended), the federal Americans with Disabilities Act of 1990 (as amended), and the federal Employee Retirement Income Security Act of 1974 (as amended).</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M188"></a>Notwithstanding the foregoing, I understand that the following rights or claims are not included in my Release: (a) any rights or claims for indemnification I may have
      pursuant to any written indemnification agreement with the Company or its affiliate to which I am a party; the charter, bylaws, or operating agreements of the Company or its affiliate; or under applicable law; or (b) any rights which cannot be waived
      as a matter of law. In addition, I understand that nothing in this Release prevents me from filing, cooperating with, or participating in any proceeding before the Equal Employment Opportunity Commission, or the Department of Labor, except that I
      hereby waive my right to any monetary benefits in connection with any such claim, charge or proceeding. I hereby represent and warrant that, other than the claims identified in this paragraph, I am not aware of any claims I have or might have that
      are not included in the Release.</div>
    <div>&#160;</div>
    <div>
      <hr noshade="noshade" align="left" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto 0px 0px; height: 2px; width: 20%; color: #000000;">
      <div> <br>
      </div>
    </div>
    <div>
      <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">7</sup> For Massachusetts employees.</div>
      <div> <br>
      </div>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M189"></a>I hereby represent that I have been paid all compensation owed and for all hours worked; I have received all the leave and leave benefits and protections for which I am
      eligible pursuant to the Family and Medical Leave Act, or otherwise; and I have not suffered any on-the-job injury for which I have not already filed a workers&#8217; compensation claim.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">[</font><font style="font-size: 10pt;">I represent that I am not aware of any claim by me other than the claims that are released by
        this Release. I acknowledge that I may hereafter discover claims or facts in addition to or different than those which I now know or believe to exist with respect to the subject matter of this Release and which, if known or suspected at the time of
        entering into this Release, may have materially affected this Release and my decision to enter into it. Nevertheless, I hereby waive any right, claim or cause of action that might arise as a result of such different or additional claims or facts
        and I hereby expressly waive any and all rights and benefits confirmed upon me by the provisions of California Civil Code Section 1542, which provides as set forth below, as well as under any other statute or common law principles of similar
        effect:</font></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS THAT THE CREDITOR OR RELEASING PARTY DOES NOT KNOW OR SUSPECT TO EXIST IN HIS OR HER FAVOR AT THE TIME OF EXECUTING THE RELEASE AND THAT, IF KNOWN BY HIM
      OR HER, WOULD HAVE MATERIALLY AFFECTED HIS OR HER SETTLEMENT WITH THE DEBTOR OR RELEASED PARTY.&#8221;<font style="font-weight: bold;">]</font><sup style="font-weight: bold; vertical-align: text-top; line-height: 1; font-size: smaller;">8</sup></div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">I agree not to disparage the Company and its affiliates,&#160; and the Company&#8217;s and its affiliates&#8217; officers, directors, employees, shareholders, investors and agents, in any manner likely to be harmful
      to them or their business, business reputation or personal reputation; provided that I may respond accurately and fully to any question, inquiry or request for information when required by legal process or as part of a government investigation.&#160;
      Notwithstanding the foregoing, nothing in this Release shall limit my right to voluntarily communicate with the Equal Employment Opportunity Commission, United States Department of Labor, the National Labor Relations Board, the Securities and
      Exchange Commission, other federal government agency or similar state or local agency or to discuss the terms and conditions of my employment with others to the extent expressly permitted by Section 7 of the National Labor Relations Act.</div>
    <div>&#160;<br>
      <div>
        <hr noshade="noshade" align="left" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto 0px 0px; height: 2px; width: 20%; color: #000000;"></div>
      <div><br>
      </div>
      <div>
        <div><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">8</sup> For California employees.</div>
      </div>
      <br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="page-break-after: always;" id="DSPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;">I agree that for the one (1) year period after the date my employment ends, I will not, as an officer, director, employee, consultant, owner, partner, or in any other capacity, either directly or
      through others, solicit, induce, encourage, or participate in soliciting, inducing or encouraging any employee, consultant, or independent contractor of Company to terminate his, her or its relationship with Company or its Affiliates, even if I did
      not initiate the discussion or seek out the contact.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><a name="z_DV_M190"></a>I acknowledge that to become effective, I must sign and return this Release to the Company so that it is received not later than fourteen (14) days following the date it is
      provided to me.</div>
    <div>&#160;</div>
    <div>
      <div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

            <tr>
              <td style="width: 50%; vertical-align: top;">&#160;</td>
              <td style="width: 50%; vertical-align: top;">
                <div style="font-variant: small-caps; font-weight: bold;">Participant:</div>
              </td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
              <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
              <td style="width: 50%; vertical-align: top;" rowspan="1">
                <div style="text-align: center; font-style: italic;">(Signature)</div>
              </td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
              </td>
              <td style="width: 50%; vertical-align: top;" rowspan="1">
                <div>Name:</div>
              </td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1"><br>
              </td>
              <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1"><br>
              </td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
              <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
              </td>
              <td style="width: 50%; vertical-align: top;" rowspan="1">
                <div>Date:</div>
              </td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top; padding-bottom: 2px;" rowspan="1"><br>
              </td>
              <td style="width: 50%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1"><br>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
  </div>
  <div><br>
  </div>
  <div>
    <hr noshade="noshade" align="center" style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;"></div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>3
<FILENAME>ex31_1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using EDGARfilings PROfile 8.2.0.0
         Copyright 1995 - 2022 Broadridge -->
  </head><body style="font-family: 'Times New Roman'; 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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z978e3b883c9248329f60bbe13b70cb38"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="za90f4570366843acba0c3c4cff226471"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z72fa4389311846379cbc19fcc6f3ca95"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="ze764b952d2ea46e88cc859609d0c613a"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zbdde8b90a8ed45869f442e288bf2931f"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z6e701e3f910a4c71b3b0602a3ff613ac"><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;">b)</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 internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zb14e911f18544b32856e3c23f579f934"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z62bd13f0c7b84fd1b177d209485f573c"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0177a34b47d24a3c89eb1db03161a129"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z0189f2eb0ae646728b9aaf37cadba8fc"><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;">All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant&#8217;s ability to record, process, summarize and report financial information; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z2bf270eaa82c411984f682ac5cb855b3"><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;">b)</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;">Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant&#8217;s internal control over financial reporting.</div></td></tr></table><div style="text-align: justify; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</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'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zdb825b098ba645eca4061193b8bb8ebb"><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated: May 4, 2022</div></td><td style="width: 72.41%; 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: 27.59%; 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: 72.41%; 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: 27.59%; 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: 72.41%; 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: 27.59%; 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: 72.41%; 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: 27.59%; 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: 72.41%; 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>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.2
<SEQUENCE>4
<FILENAME>ex31_2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using EDGARfilings PROfile 8.2.0.0
         Copyright 1995 - 2022 Broadridge -->
  </head><body style="font-family: 'Times New Roman'; 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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z73e41eb6820744e49dfbb6fad5eaa833"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="za6c1217b591b4d2383b9e45ff3eb0d8b"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="ze24dcbbdba6842a49d9d6517f8bdd152"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z98f84c80b5fa43a884a2bf24b744041b"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zb17a54ee8fa348209aa0c19c692dc961"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z177e3b69935a4c94a975e0f2d583658a"><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;">b)</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 internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd58ef2d27de245f991723b1f2d4edce4"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z2766ebd135044a15ac28fddd4bf257f7"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zcd731e9b8abf46e1a8d2277cda83c463"><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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z5405b12e948840c2a1b3379376c28420"><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;">All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant&#8217;s ability to record, process, summarize and report financial information; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd82edb55939444c3b8498072c9d87264"><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;">b)</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;">Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant&#8217;s internal control over financial reporting.</div></td></tr></table><div><br></div><div><br></div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z971d52cd974a44b195c4081b33a6574f"><tr><td style="width: 27.45%; 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 4, 2022</div></td><td style="width: 72.55%; 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: 27.45%; 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: 72.55%; 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 nowrap="nowrap" style="width: 27.45%; 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: 72.55%; 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: 27.45%; 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: 72.55%; 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: 27.45%; 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: 72.55%; 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>
<TYPE>EX-32.1
<SEQUENCE>5
<FILENAME>ex32_1.htm
<DESCRIPTION>EXHIBIT 32.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using EDGARfilings PROfile 8.2.0.0
         Copyright 1995 - 2022 Broadridge -->
  </head><body style="font-family: 'Times New Roman'; 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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc40f1638bd7547e8af5e2a4b748a4365"><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, 2022, 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'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z30e21a49b34f468f9797246ce3e8e217"><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'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zf492225ce71746f29353c0be6eeeb61d"><tr><td style="width: 23.41%; 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 4, 2022</div></td><td style="width: 29.86%; 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: 23.47%; 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: 23.26%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 23.41%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 29.86%; 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: 23.47%; 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: 23.26%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 23.41%; vertical-align: bottom; 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: 29.86%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td nowrap="nowrap" style="width: 23.47%; 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: 23.26%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 23.41%; vertical-align: top;"><div style="text-align: left; color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div></td><td style="width: 29.86%; 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: 23.47%; 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: 23.26%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 23.41%; 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: 29.86%; 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: 23.47%; 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: 23.26%; vertical-align: top;">&#160;</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>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.SCH
<SEQUENCE>6
<FILENAME>ions-20220331.xsd
<DESCRIPTION>XBRL TAXONOMY EXTENSION SCHEMA
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 8.0.0.0 Broadridge-->
<xs:schema targetNamespace="http://ionispharma.com/20220331" elementFormDefault="qualified" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:ions="http://ionispharma.com/20220331" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:us-types="http://fasb.org/us-types/2021-01-31" xmlns:srt-types="http://fasb.org/srt-types/2021-01-31" xmlns:dei="http://xbrl.sec.gov/dei/2021q4" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2020-01-21">
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xlink:type="simple" xlink:href="ions-20220331_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="ions-20220331_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="ions-20220331_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="ions-20220331_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:roleType roleURI="http://ionispharma.com/role/DocumentAndEntityInformation" id="DocumentAndEntityInformation">
        <link:definition>000100 - Document - Document and Entity Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/CondensedConsolidatedBalanceSheets" id="CondensedConsolidatedBalanceSheets">
        <link:definition>010000 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical" id="CondensedConsolidatedBalanceSheetsParenthetical">
        <!--Parent Role: CONDENSED CONSOLIDATED BALANCE SHEETS-->
        <link:definition>010100 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations" id="CondensedConsolidatedStatementsOfOperations">
        <link:definition>020000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss" id="CondensedConsolidatedStatementsOfComprehensiveLoss">
        <link:definition>030000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity" id="CondensedConsolidatedStatementsOfStockholdersEquity">
        <link:definition>040000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows" id="CondensedConsolidatedStatementsOfCashFlows">
        <link:definition>050000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/BasisOfPresentation" id="BasisOfPresentation">
        <link:definition>060100 - Disclosure - Basis of Presentation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPolicies" id="SignificantAccountingPolicies">
        <link:definition>060200 - Disclosure - Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/Investments" id="Investments">
        <link:definition>060300 - Disclosure - Investments</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/FairValueMeasurements" id="FairValueMeasurements">
        <link:definition>060400 - Disclosure - Fair Value Measurements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxes" id="IncomeTaxes">
        <link:definition>060500 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreements" id="CollaborativeArrangementsAndLicensingAgreements">
        <link:definition>060600 - Disclosure - Collaborative Arrangements and Licensing Agreements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/ConvertibleDebt" id="ConvertibleDebt">
        <link:definition>060700 - Disclosure - Convertible Debt</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/BasisOfPresentationPolicies" id="BasisOfPresentationPolicies">
        <!--Parent Role: Basis of Presentation-->
        <link:definition>070100 - Disclosure - Basis of Presentation (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesPolicies" id="SignificantAccountingPoliciesPolicies">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>070200 - Disclosure - Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesTables" id="SignificantAccountingPoliciesTables">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>080200 - Disclosure - Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/InvestmentsTables" id="InvestmentsTables">
        <!--Parent Role: Investments-->
        <link:definition>080300 - Disclosure - Investments (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/FairValueMeasurementsTables" id="FairValueMeasurementsTables">
        <!--Parent Role: Fair Value Measurements-->
        <link:definition>080400 - Disclosure - Fair Value Measurements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsTables" id="CollaborativeArrangementsAndLicensingAgreementsTables">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>080600 - Disclosure - Collaborative Arrangements and Licensing Agreements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/ConvertibleDebtTables" id="ConvertibleDebtTables">
        <!--Parent Role: Convertible Debt-->
        <link:definition>080700 - Disclosure - Convertible Debt (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails" id="SignificantAccountingPoliciesRevenueRecognitionDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090200 - Disclosure - Significant Accounting Policies, Revenue Recognition (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails" id="SignificantAccountingPoliciesContractsReceivableDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090202 - Disclosure - Significant Accounting Policies, Contracts Receivable (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesDeferredRevenueDetails" id="SignificantAccountingPoliciesDeferredRevenueDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090204 - Disclosure - Significant Accounting Policies, Deferred Revenue (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" id="SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090208 - Disclosure - Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails" id="SignificantAccountingPoliciesInventoryValuationDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090210 - Disclosure - Significant Accounting Policies, Inventory Valuation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails" id="SignificantAccountingPoliciesLeasesDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090212 - Disclosure - Significant Accounting Policies, Leases (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails" id="SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090214 - Disclosure - Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails" id="SignificantAccountingPoliciesConvertibleDebtDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090216 - Disclosure - Significant Accounting Policies, Convertible Debt (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesSegmentInformationDetails" id="SignificantAccountingPoliciesSegmentInformationDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090218 - Disclosure - Significant Accounting Policies, Segment Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails" id="SignificantAccountingPoliciesStockbasedCompensationExpenseDetails">
        <!--Parent Role: Significant Accounting Policies-->
        <link:definition>090220 - Disclosure - Significant Accounting Policies, Stock-Based Compensation Expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" id="InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails">
        <!--Parent Role: Investments-->
        <link:definition>090300 - Disclosure - Investments, Contract Maturity of Available-for-Sale Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails" id="InvestmentsSummaryOfInvestmentsDetails">
        <!--Parent Role: Investments-->
        <link:definition>090302 - Disclosure - Investments, Summary of Investments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails" id="InvestmentsInvestmentsTemporarilyImpairedDetails">
        <!--Parent Role: Investments-->
        <link:definition>090304 - Disclosure - Investments, Investments Temporarily Impaired (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/FairValueMeasurementsDetails" id="FairValueMeasurementsDetails">
        <!--Parent Role: Fair Value Measurements-->
        <link:definition>090400 - Disclosure - Fair Value Measurements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxesDetails" id="IncomeTaxesDetails">
        <!--Parent Role: Income Taxes-->
        <link:definition>090500 - Disclosure - Income Taxes (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails" id="CollaborativeArrangementsAndLicensingAgreementsDetails">
        <!--Parent Role: Collaborative Arrangements and Licensing Agreements-->
        <link:definition>090600 - Disclosure - Collaborative Arrangements and Licensing Agreements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://ionispharma.com/role/ConvertibleDebtDetails" id="ConvertibleDebtDetails">
        <!--Parent Role: Convertible Debt-->
        <link:definition>090700 - Disclosure - Convertible Debt (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xs:appinfo>
  </xs:annotation>
  <xs:import namespace="http://fasb.org/us-gaap/2021-01-31" schemaLocation="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/dei/2021q4" schemaLocation="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/country/2021" schemaLocation="https://xbrl.sec.gov/country/2021/country-2021.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/currency/2021" schemaLocation="https://xbrl.sec.gov/currency/2021/currency-2021.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/exch/2021" schemaLocation="https://xbrl.sec.gov/exch/2021/exch-2021.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/naics/2021" schemaLocation="https://xbrl.sec.gov/naics/2021/naics-2021.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/sic/2021" schemaLocation="https://xbrl.sec.gov/sic/2021/sic-2021.xsd" />
  <xs:import namespace="http://www.xbrl.org/2009/role/negated" schemaLocation="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd" />
  <xs:import namespace="http://www.xbrl.org/2009/role/net" schemaLocation="http://www.xbrl.org/lrr/role/net-2009-12-16.xsd" />
  <xs:import namespace="http://xbrl.sec.gov/stpr/2021" schemaLocation="https://xbrl.sec.gov/stpr/2021/stpr-2021.xsd" />
  <xs:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd" />
  <xs:import namespace="http://www.xbrl.org/2004/ref" schemaLocation="http://www.xbrl.org/2004/ref-2004-08-10.xsd" />
  <xs:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd" />
  <xs:import namespace="http://fasb.org/us-types/2021-01-31" schemaLocation="https://xbrl.fasb.org/us-gaap/2021/elts/us-types-2021-01-31.xsd" />
  <xs:import namespace="http://www.xbrl.org/2009/arcrole/fact-explanatoryFact" schemaLocation="http://www.xbrl.org/lrr/arcrole/factExplanatory-2009-12-16.xsd" />
  <xs:import namespace="http://fasb.org/srt/2021-01-31" schemaLocation="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd" />
  <xs:import namespace="http://fasb.org/srt-types/2021-01-31" schemaLocation="https://xbrl.fasb.org/srt/2021/elts/srt-types-2021-01-31.xsd" />
  <xs:import namespace="http://www.xbrl.org/dtr/type/2020-01-21" schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/types.xsd" />
  <xs:element name="LongTermObligationsExcludingConvertibleDebtNoncurrent" id="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="LongTermObligationsExcludingConvertibleDebtCurrent" id="ions_LongTermObligationsExcludingConvertibleDebtCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="ConvertibleSeniorNotes0125PercentMember" id="ions_ConvertibleSeniorNotes0125PercentMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ConvertibleSeniorNotes0PercentMember" id="ions_ConvertibleSeniorNotes0PercentMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" id="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" id="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="MaximumContractMaturityPeriodRange1" id="ions_MaximumContractMaturityPeriodRange1" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="MaximumContractMaturityPeriodRange2" id="ions_MaximumContractMaturityPeriodRange2" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="MaximumContractMaturityPeriodRange3" id="ions_MaximumContractMaturityPeriodRange3" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="ResearchDevelopmentAndPatentExpensesMember" id="ions_ResearchDevelopmentAndPatentExpensesMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" id="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" id="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ShareBasedPaymentArrangementBoardOfDirectorMember" id="ions_ShareBasedPaymentArrangementBoardOfDirectorMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="ResearchAndDevelopmentRevenueMember" id="ions_ResearchAndDevelopmentRevenueMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ResearchDevelopmentAndPatentExpense" id="ions_ResearchDevelopmentAndPatentExpense" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="EplontersenJointDevelopmentRevenueMember" id="ions_EplontersenJointDevelopmentRevenueMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CommercialMember" id="ions_CommercialMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="SpinrazaRoyaltiesMember" id="ions_SpinrazaRoyaltiesMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="LicensingAndOtherRoyaltiesMember" id="ions_LicensingAndOtherRoyaltiesMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeAgreementRevenueMember" id="ions_CollaborativeAgreementRevenueMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NonCashCapitalAndPatentExpenditures" id="ions_NonCashCapitalAndPatentExpenditures" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" />
  <xs:element name="CollaborativeArrangementsAndLicensingAgreementsAbstract" id="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="BicycleTherapeuticsPlcMember" id="ions_BicycleTherapeuticsPlcMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ProqrTherapeuticsNVMember" id="ions_ProqrTherapeuticsNVMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" id="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="SecuritiesWithMaturityOfOneYearOrLessMember" id="ions_SecuritiesWithMaturityOfOneYearOrLessMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="SecuritiesWithMaturityOfMoreThanOneYearMember" id="ions_SecuritiesWithMaturityOfMoreThanOneYearMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" />
  <xs:element name="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" />
  <xs:element name="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" />
  <xs:element name="EquitySecuritiesPubliclyTradedCompaniesMember" id="ions_EquitySecuritiesPubliclyTradedCompaniesMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="EquitySecuritiesPrivateCompaniesMember" id="ions_EquitySecuritiesPrivateCompaniesMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="AstrazenecaCollaborationEplontersenMember" id="ions_AstrazenecaCollaborationEplontersenMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfAgreementsWithCollaborationPartner" id="ions_NumberOfAgreementsWithCollaborationPartner" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="UpfrontPaymentReceived" id="ions_UpfrontPaymentReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="BiogenCollaboration2013StrategicNeurologyMember" id="ions_BiogenCollaboration2013StrategicNeurologyMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="Ion859Member" id="ions_Ion859Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfTargetsAdvanced" id="ions_NumberOfTargetsAdvanced" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="Ion306Member" id="ions_Ion306Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="BiogenCollaboration2018StrategicNeurologyMember" id="ions_BiogenCollaboration2018StrategicNeurologyMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="AlnylamCollaborationMember" id="ions_AlnylamCollaborationMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfMaterialComponents" id="ions_NumberOfMaterialComponents" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="RevenueFromContractWithCustomerTransactionPriceAdditions" id="ions_RevenueFromContractWithCustomerTransactionPriceAdditions" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" />
  <xs:element name="BiogenIncMember" id="ions_BiogenIncMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="RevenueFromContractWithCustomerTransactionPrice" id="ions_RevenueFromContractWithCustomerTransactionPrice" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="LesseeOperatingLeaseFreeRentPeriod" id="ions_LesseeOperatingLeaseFreeRentPeriod" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="ConvertibleSeniorNotes1PercentMember" id="ions_ConvertibleSeniorNotes1PercentMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ClinicalRawMaterialsMember" id="ions_ClinicalRawMaterialsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CommercialRawMaterialsMember" id="ions_CommercialRawMaterialsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NextPotentialPayment" id="ions_NextPotentialPayment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="BiogenCollaborationsMember" id="ions_BiogenCollaborationsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CollaborativeArrangementAndLicensingAgreementAbstract" id="ions_CollaborativeArrangementAndLicensingAgreementAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="CumulativePaymentsReceived" id="ions_CumulativePaymentsReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" />
  <xs:element name="Ion541Member" id="ions_Ion541Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="PeriodAfterBillingWhenPaymentIsReceived" id="ions_PeriodAfterBillingWhenPaymentIsReceived" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="SignificantPartnersAbstract" id="ions_SignificantPartnersAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="NumberOfSignificantCustomers" id="ions_NumberOfSignificantCustomers" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="TwoSignificantCustomersMember" id="ions_TwoSignificantCustomersMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="AmortizationPeriodForResearchAndDevelopmentExpenditures" id="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="ConvertibleNotesDisclosureTable" id="ions_ConvertibleNotesDisclosureTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ConvertibleNotesDisclosureLineItems" id="ions_ConvertibleNotesDisclosureLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" />
  <xs:element name="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" type="dtr-types:perShareItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="DebtInstrumentConvertibleSharesSubjectToConversion" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" />
  <xs:element name="CallSpread" id="ions_CallSpread" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" />
</xs:schema>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.CAL
<SEQUENCE>7
<FILENAME>ions-20220331_cal.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION CALCULATION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 8.0.0.0 Broadridge-->
<link:linkbase xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance">
  <link:roleRef roleURI="http://ionispharma.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#FairValueMeasurementsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsInvestmentsTemporarilyImpairedDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsSummaryOfInvestmentsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesInventoryValuationDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfCashFlows" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfComprehensiveLoss" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfOperations" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedBalanceSheets" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedBalanceSheets" />
  <link:calculationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedBalanceSheets">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Assets" xlink:label="Assets" xlink:title="Assets" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="FiniteLivedIntangibleAssetsNet" xlink:title="FiniteLivedIntangibleAssetsNet" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Assets" xlink:to="FiniteLivedIntangibleAssetsNet" xlink:title="calculation: Assets to FiniteLivedIntangibleAssetsNet" order="4.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="OtherAssetsNoncurrent" xlink:title="OtherAssetsNoncurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Assets" xlink:to="OtherAssetsNoncurrent" xlink:title="calculation: Assets to OtherAssetsNoncurrent" order="6.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="AssetsCurrent" xlink:title="AssetsCurrent" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsCurrent" xlink:label="OtherAssetsCurrent" xlink:title="OtherAssetsCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AssetsCurrent" xlink:to="OtherAssetsCurrent" xlink:title="calculation: AssetsCurrent to OtherAssetsCurrent" order="5.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AssetsCurrent" xlink:to="InventoryNet" xlink:title="calculation: AssetsCurrent to InventoryNet" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:title="AvailableForSaleSecuritiesDebtSecuritiesCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AssetsCurrent" xlink:to="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:title="calculation: AssetsCurrent to AvailableForSaleSecuritiesDebtSecuritiesCurrent" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="CashAndCashEquivalentsAtCarryingValue" xlink:title="CashAndCashEquivalentsAtCarryingValue" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AssetsCurrent" xlink:to="CashAndCashEquivalentsAtCarryingValue" xlink:title="calculation: AssetsCurrent to CashAndCashEquivalentsAtCarryingValue" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerAssetNetCurrent" xlink:label="ContractWithCustomerAssetNetCurrent" xlink:title="ContractWithCustomerAssetNetCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AssetsCurrent" xlink:to="ContractWithCustomerAssetNetCurrent" xlink:title="calculation: AssetsCurrent to ContractWithCustomerAssetNetCurrent" order="2.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Assets" xlink:to="AssetsCurrent" xlink:title="calculation: Assets to AssetsCurrent" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="PropertyPlantAndEquipmentNet" xlink:title="PropertyPlantAndEquipmentNet" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Assets" xlink:to="PropertyPlantAndEquipmentNet" xlink:title="calculation: Assets to PropertyPlantAndEquipmentNet" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="EmployeeRelatedLiabilitiesCurrent" xlink:title="EmployeeRelatedLiabilitiesCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesCurrent" xlink:to="EmployeeRelatedLiabilitiesCurrent" xlink:title="calculation: LiabilitiesCurrent to EmployeeRelatedLiabilitiesCurrent" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="AccountsPayableCurrent" xlink:title="AccountsPayableCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesCurrent" xlink:to="AccountsPayableCurrent" xlink:title="calculation: LiabilitiesCurrent to AccountsPayableCurrent" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="ContractWithCustomerLiabilityCurrent" xlink:title="ContractWithCustomerLiabilityCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesCurrent" xlink:to="ContractWithCustomerLiabilityCurrent" xlink:title="calculation: LiabilitiesCurrent to ContractWithCustomerLiabilityCurrent" order="7.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="AccruedLiabilitiesCurrent" xlink:title="AccruedLiabilitiesCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesCurrent" xlink:to="AccruedLiabilitiesCurrent" xlink:title="calculation: LiabilitiesCurrent to AccruedLiabilitiesCurrent" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LongTermObligationsExcludingConvertibleDebtCurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesCurrent" xlink:to="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:title="calculation: LiabilitiesCurrent to LongTermObligationsExcludingConvertibleDebtCurrent" order="6.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedIncomeTaxesCurrent" xlink:label="AccruedIncomeTaxesCurrent" xlink:title="AccruedIncomeTaxesCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesCurrent" xlink:to="AccruedIncomeTaxesCurrent" xlink:title="calculation: LiabilitiesCurrent to AccruedIncomeTaxesCurrent" order="4.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Liabilities" xlink:to="LiabilitiesCurrent" xlink:title="calculation: Liabilities to LiabilitiesCurrent" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="ContractWithCustomerLiabilityNoncurrent" xlink:title="ContractWithCustomerLiabilityNoncurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Liabilities" xlink:to="ContractWithCustomerLiabilityNoncurrent" xlink:title="calculation: Liabilities to ContractWithCustomerLiabilityNoncurrent" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleDebtNoncurrent" xlink:label="ConvertibleDebtNoncurrent" xlink:title="ConvertibleDebtNoncurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Liabilities" xlink:to="ConvertibleDebtNoncurrent" xlink:title="calculation: Liabilities to ConvertibleDebtNoncurrent" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtNoncurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Liabilities" xlink:to="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:title="calculation: Liabilities to LongTermObligationsExcludingConvertibleDebtNoncurrent" order="4.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermLoansFromBank" xlink:label="LongTermLoansFromBank" xlink:title="LongTermLoansFromBank" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="Liabilities" xlink:to="LongTermLoansFromBank" xlink:title="calculation: Liabilities to LongTermLoansFromBank" order="6.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="Liabilities" xlink:title="calculation: LiabilitiesAndStockholdersEquity to Liabilities" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="StockholdersEquity" xlink:title="StockholdersEquity" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:title="AccumulatedOtherComprehensiveIncomeLossNetOfTax" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="StockholdersEquity" xlink:to="AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:title="calculation: StockholdersEquity to AccumulatedOtherComprehensiveIncomeLossNetOfTax" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="AdditionalPaidInCapitalCommonStock" xlink:title="AdditionalPaidInCapitalCommonStock" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="StockholdersEquity" xlink:to="AdditionalPaidInCapitalCommonStock" xlink:title="calculation: StockholdersEquity to AdditionalPaidInCapitalCommonStock" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="RetainedEarningsAccumulatedDeficit" xlink:title="RetainedEarningsAccumulatedDeficit" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="StockholdersEquity" xlink:to="RetainedEarningsAccumulatedDeficit" xlink:title="calculation: StockholdersEquity to RetainedEarningsAccumulatedDeficit" order="4.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockValue" xlink:label="CommonStockValue" xlink:title="CommonStockValue" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="StockholdersEquity" xlink:to="CommonStockValue" xlink:title="calculation: StockholdersEquity to CommonStockValue" order="1.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="StockholdersEquity" xlink:title="calculation: LiabilitiesAndStockholdersEquity to StockholdersEquity" order="2.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:title="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="OtherNonoperatingIncomeExpense" xlink:title="OtherNonoperatingIncomeExpense" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="OtherNonoperatingIncomeExpense" xlink:title="calculation: IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest to OtherNonoperatingIncomeExpense" order="10.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="InvestmentIncomeNet" xlink:title="calculation: IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest to InvestmentIncomeNet" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="InterestExpense" xlink:title="calculation: IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest to InterestExpense" order="4.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="OperatingIncomeLoss" xlink:title="OperatingIncomeLoss" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchDevelopmentAndPatentExpense" xlink:label="ResearchDevelopmentAndPatentExpense" xlink:title="ResearchDevelopmentAndPatentExpense" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="CostsAndExpenses" xlink:to="ResearchDevelopmentAndPatentExpense" xlink:title="calculation: CostsAndExpenses to ResearchDevelopmentAndPatentExpense" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="SellingGeneralAndAdministrativeExpense" xlink:title="SellingGeneralAndAdministrativeExpense" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="CostsAndExpenses" xlink:to="SellingGeneralAndAdministrativeExpense" xlink:title="calculation: CostsAndExpenses to SellingGeneralAndAdministrativeExpense" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="CostOfGoodsAndServicesSold" xlink:title="CostOfGoodsAndServicesSold" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="CostsAndExpenses" xlink:to="CostOfGoodsAndServicesSold" xlink:title="calculation: CostsAndExpenses to CostOfGoodsAndServicesSold" order="1.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="OperatingIncomeLoss" xlink:to="CostsAndExpenses" xlink:title="calculation: OperatingIncomeLoss to CostsAndExpenses" order="3.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="OperatingIncomeLoss" xlink:to="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="calculation: OperatingIncomeLoss to RevenueFromContractWithCustomerExcludingAssessedTax" order="2.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="OperatingIncomeLoss" xlink:title="calculation: IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest to OperatingIncomeLoss" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnInvestments" xlink:label="GainLossOnInvestments" xlink:title="GainLossOnInvestments" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="GainLossOnInvestments" xlink:title="calculation: IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest to GainLossOnInvestments" order="8.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetIncomeLoss" xlink:to="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:title="calculation: NetIncomeLoss to IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="IncomeTaxExpenseBenefit" xlink:title="IncomeTaxExpenseBenefit" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetIncomeLoss" xlink:to="IncomeTaxExpenseBenefit" xlink:title="calculation: NetIncomeLoss to IncomeTaxExpenseBenefit" order="1.0" weight="-1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="ComprehensiveIncomeNetOfTax" xlink:title="ComprehensiveIncomeNetOfTax" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="calculation: ComprehensiveIncomeNetOfTax to OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:title="calculation: ComprehensiveIncomeNetOfTax to OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="NetIncomeLoss" xlink:title="calculation: ComprehensiveIncomeNetOfTax to NetIncomeLoss" order="0.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="NetCashProvidedByUsedInFinancingActivities" xlink:title="NetCashProvidedByUsedInFinancingActivities" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:label="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="calculation: NetCashProvidedByUsedInFinancingActivities to ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="calculation: NetCashProvidedByUsedInFinancingActivities to PaymentsRelatedToTaxWithholdingForShareBasedCompensation" order="11.0" weight="-1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="NetCashProvidedByUsedInFinancingActivities" xlink:title="calculation: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect to NetCashProvidedByUsedInFinancingActivities" order="5.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="NetCashProvidedByUsedInInvestingActivities" xlink:title="NetCashProvidedByUsedInInvestingActivities" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="calculation: NetCashProvidedByUsedInInvestingActivities to ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireIntangibleAssets" xlink:label="PaymentsToAcquireIntangibleAssets" xlink:title="PaymentsToAcquireIntangibleAssets" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="PaymentsToAcquireIntangibleAssets" xlink:title="calculation: NetCashProvidedByUsedInInvestingActivities to PaymentsToAcquireIntangibleAssets" order="5.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="PaymentsToAcquireAvailableForSaleSecuritiesDebt" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="calculation: NetCashProvidedByUsedInInvestingActivities to PaymentsToAcquireAvailableForSaleSecuritiesDebt" order="1.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="PaymentsToAcquirePropertyPlantAndEquipment" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInInvestingActivities" xlink:to="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="calculation: NetCashProvidedByUsedInInvestingActivities to PaymentsToAcquirePropertyPlantAndEquipment" order="3.0" weight="-1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="NetCashProvidedByUsedInInvestingActivities" xlink:title="calculation: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect to NetCashProvidedByUsedInInvestingActivities" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="NetCashProvidedByUsedInOperatingActivities" xlink:title="NetCashProvidedByUsedInOperatingActivities" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ImpairmentOfIntangibleAssetsFinitelived" xlink:label="ImpairmentOfIntangibleAssetsFinitelived" xlink:title="ImpairmentOfIntangibleAssetsFinitelived" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="ImpairmentOfIntangibleAssetsFinitelived" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to ImpairmentOfIntangibleAssetsFinitelived" order="15.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfFinancingCosts" xlink:label="AmortizationOfFinancingCosts" xlink:title="AmortizationOfFinancingCosts" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="AmortizationOfFinancingCosts" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to AmortizationOfFinancingCosts" order="5.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="ShareBasedCompensation" xlink:title="ShareBasedCompensation" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="ShareBasedCompensation" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to ShareBasedCompensation" order="8.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="NetIncomeLoss" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to NetIncomeLoss" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="IncreaseDecreaseInInventories" xlink:title="IncreaseDecreaseInInventories" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="IncreaseDecreaseInInventories" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to IncreaseDecreaseInInventories" order="19.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="IncreaseDecreaseInAccountsPayable" xlink:title="IncreaseDecreaseInAccountsPayable" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="IncreaseDecreaseInAccountsPayable" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to IncreaseDecreaseInAccountsPayable" order="22.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:label="AmortizationOfIntangibleAssets" xlink:title="AmortizationOfIntangibleAssets" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="AmortizationOfIntangibleAssets" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to AmortizationOfIntangibleAssets" order="3.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerAsset" xlink:label="IncreaseDecreaseInContractWithCustomerAsset" xlink:title="IncreaseDecreaseInContractWithCustomerAsset" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="IncreaseDecreaseInContractWithCustomerAsset" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to IncreaseDecreaseInContractWithCustomerAsset" order="18.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability" xlink:label="IncreaseDecreaseInContractWithCustomerLiability" xlink:title="IncreaseDecreaseInContractWithCustomerLiability" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="IncreaseDecreaseInContractWithCustomerLiability" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to IncreaseDecreaseInContractWithCustomerLiability" order="25.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:label="IncreaseDecreaseInOtherOperatingAssets" xlink:title="IncreaseDecreaseInOtherOperatingAssets" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="IncreaseDecreaseInOtherOperatingAssets" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to IncreaseDecreaseInOtherOperatingAssets" order="20.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:label="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to IncreaseDecreaseInOtherEmployeeRelatedLiabilities" order="23.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherCurrentLiabilities" xlink:label="IncreaseDecreaseInOtherCurrentLiabilities" xlink:title="IncreaseDecreaseInOtherCurrentLiabilities" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="IncreaseDecreaseInOtherCurrentLiabilities" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to IncreaseDecreaseInOtherCurrentLiabilities" order="24.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:label="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:title="AccretionAmortizationOfDiscountsAndPremiumsInvestments" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to AccretionAmortizationOfDiscountsAndPremiumsInvestments" order="4.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RealizedInvestmentGainsLosses" xlink:label="RealizedInvestmentGainsLosses" xlink:title="RealizedInvestmentGainsLosses" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="RealizedInvestmentGainsLosses" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to RealizedInvestmentGainsLosses" order="12.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Depreciation" xlink:label="Depreciation" xlink:title="Depreciation" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="Depreciation" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to Depreciation" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnDispositionOfAssets" xlink:label="GainLossOnDispositionOfAssets" xlink:title="GainLossOnDispositionOfAssets" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="GainLossOnDispositionOfAssets" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to GainLossOnDispositionOfAssets" order="14.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:label="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to OperatingLeaseRightOfUseAssetAmortizationExpense" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:label="IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:title="IncreaseDecreaseInAccruedIncomeTaxesPayable" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="NetCashProvidedByUsedInOperatingActivities" xlink:to="IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:title="calculation: NetCashProvidedByUsedInOperatingActivities to IncreaseDecreaseInAccruedIncomeTaxesPayable" order="21.0" weight="1.0" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="NetCashProvidedByUsedInOperatingActivities" xlink:title="calculation: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect to NetCashProvidedByUsedInOperatingActivities" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents" xlink:label="EffectOfExchangeRateOnCashAndCashEquivalents" xlink:title="EffectOfExchangeRateOnCashAndCashEquivalents" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="EffectOfExchangeRateOnCashAndCashEquivalents" xlink:title="calculation: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect to EffectOfExchangeRateOnCashAndCashEquivalents" order="4.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryFinishedGoods" xlink:label="InventoryFinishedGoods" xlink:title="InventoryFinishedGoods" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="InventoryNet" xlink:to="InventoryFinishedGoods" xlink:title="calculation: InventoryNet to InventoryFinishedGoods" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryRawMaterials" xlink:label="InventoryRawMaterials" xlink:title="InventoryRawMaterials" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="InventoryNet" xlink:to="InventoryRawMaterials" xlink:title="calculation: InventoryNet to InventoryRawMaterials" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="InventoryNet" xlink:to="InventoryWorkInProcess" xlink:title="calculation: InventoryNet to InventoryWorkInProcess" order="1.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails">
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="calculation: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="calculation: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="calculation: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" order="3.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:title="AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="AvailableForSaleSecuritiesDebtSecurities" xlink:title="AvailableForSaleSecuritiesDebtSecurities" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="AvailableForSaleSecuritiesDebtSecurities" xlink:title="calculation: AvailableForSaleDebtSecuritiesAmortizedCostBasis to AvailableForSaleSecuritiesDebtSecurities" order="4.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:title="calculation: AvailableForSaleDebtSecuritiesAmortizedCostBasis to AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="calculation: AvailableForSaleDebtSecuritiesAmortizedCostBasis to AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" order="0.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:title="calculation: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" order="0.0" weight="-1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:title="calculation: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:title="calculation: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" order="1.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="calculation: DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="calculation: DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" order="1.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:label="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:title="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:title="calculation: DebtSecuritiesAvailableForSaleUnrealizedLossPosition to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:title="calculation: DebtSecuritiesAvailableForSaleUnrealizedLossPosition to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" order="1.0" weight="1.0" />
  </link:calculationLink>
  <link:calculationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/FairValueMeasurementsDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="AssetsFairValueDisclosure" xlink:title="AssetsFairValueDisclosure" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNi" xlink:label="EquitySecuritiesFvNi" xlink:title="EquitySecuritiesFvNi" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AssetsFairValueDisclosure" xlink:to="EquitySecuritiesFvNi" xlink:title="calculation: AssetsFairValueDisclosure to EquitySecuritiesFvNi" order="2.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="CashAndCashEquivalentsFairValueDisclosure" xlink:title="CashAndCashEquivalentsFairValueDisclosure" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AssetsFairValueDisclosure" xlink:to="CashAndCashEquivalentsFairValueDisclosure" xlink:title="calculation: AssetsFairValueDisclosure to CashAndCashEquivalentsFairValueDisclosure" order="0.0" weight="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="AvailableForSaleSecuritiesDebtSecurities" xlink:title="AvailableForSaleSecuritiesDebtSecurities" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="AssetsFairValueDisclosure" xlink:to="AvailableForSaleSecuritiesDebtSecurities" xlink:title="calculation: AssetsFairValueDisclosure to AvailableForSaleSecuritiesDebtSecurities" order="1.0" weight="1.0" />
  </link:calculationLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.DEF
<SEQUENCE>8
<FILENAME>ions-20220331_def.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION DEFINITION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 8.0.0.0 Broadridge-->
<link:linkbase xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:t1="http://xbrl.org/2005/xbrldt">
  <link:roleRef roleURI="http://ionispharma.com/role/ConvertibleDebtDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#ConvertibleDebtDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#CollaborativeArrangementsAndLicensingAgreementsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/IncomeTaxesDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#IncomeTaxesDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#FairValueMeasurementsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsInvestmentsTemporarilyImpairedDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsSummaryOfInvestmentsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesStockbasedCompensationExpenseDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesSegmentInformationDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesSegmentInformationDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesConvertibleDebtDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesLeasesDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesInventoryValuationDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesDeferredRevenueDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesDeferredRevenueDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesContractsReceivableDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesRevenueRecognitionDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/ConvertibleDebtTables" xlink:type="simple" xlink:href="ions-20220331.xsd#ConvertibleDebtTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsTables" xlink:type="simple" xlink:href="ions-20220331.xsd#CollaborativeArrangementsAndLicensingAgreementsTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/FairValueMeasurementsTables" xlink:type="simple" xlink:href="ions-20220331.xsd#FairValueMeasurementsTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsTables" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesTables" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesPolicies" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesPolicies" />
  <link:roleRef roleURI="http://ionispharma.com/role/BasisOfPresentationPolicies" xlink:type="simple" xlink:href="ions-20220331.xsd#BasisOfPresentationPolicies" />
  <link:roleRef roleURI="http://ionispharma.com/role/ConvertibleDebt" xlink:type="simple" xlink:href="ions-20220331.xsd#ConvertibleDebt" />
  <link:roleRef roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreements" xlink:type="simple" xlink:href="ions-20220331.xsd#CollaborativeArrangementsAndLicensingAgreements" />
  <link:roleRef roleURI="http://ionispharma.com/role/IncomeTaxes" xlink:type="simple" xlink:href="ions-20220331.xsd#IncomeTaxes" />
  <link:roleRef roleURI="http://ionispharma.com/role/FairValueMeasurements" xlink:type="simple" xlink:href="ions-20220331.xsd#FairValueMeasurements" />
  <link:roleRef roleURI="http://ionispharma.com/role/Investments" xlink:type="simple" xlink:href="ions-20220331.xsd#Investments" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPolicies" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPolicies" />
  <link:roleRef roleURI="http://ionispharma.com/role/BasisOfPresentation" xlink:type="simple" xlink:href="ions-20220331.xsd#BasisOfPresentation" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfCashFlows" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfStockholdersEquity" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfComprehensiveLoss" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfOperations" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedBalanceSheetsParenthetical" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedBalanceSheets" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedBalanceSheets" />
  <link:roleRef roleURI="http://ionispharma.com/role/DocumentAndEntityInformation" xlink:type="simple" xlink:href="ions-20220331.xsd#DocumentAndEntityInformation" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/DocumentAndEntityInformation" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedBalanceSheets">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsAbstract" xlink:label="AssetsAbstract" xlink:title="AssetsAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AssetsAbstract" xlink:title="definition: StatementLineItems to AssetsAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="LiabilitiesAndStockholdersEquityAbstract" xlink:title="definition: StatementLineItems to LiabilitiesAndStockholdersEquityAbstract" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="LiabilitiesCurrentAbstract" xlink:title="LiabilitiesCurrentAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="LiabilitiesCurrentAbstract" xlink:title="definition: StatementLineItems to LiabilitiesCurrentAbstract" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="ContractWithCustomerLiabilityNoncurrent" xlink:title="ContractWithCustomerLiabilityNoncurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ContractWithCustomerLiabilityNoncurrent" xlink:title="definition: StatementLineItems to ContractWithCustomerLiabilityNoncurrent" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleDebtNoncurrent" xlink:label="ConvertibleDebtNoncurrent" xlink:title="ConvertibleDebtNoncurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ConvertibleDebtNoncurrent" xlink:title="definition: StatementLineItems to ConvertibleDebtNoncurrent" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtNoncurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:title="definition: StatementLineItems to LongTermObligationsExcludingConvertibleDebtNoncurrent" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermLoansFromBank" xlink:label="LongTermLoansFromBank" xlink:title="LongTermLoansFromBank" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="LongTermLoansFromBank" xlink:title="definition: StatementLineItems to LongTermLoansFromBank" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="Liabilities" xlink:title="definition: StatementLineItems to Liabilities" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="StockholdersEquityAbstract" xlink:title="definition: StatementLineItems to StockholdersEquityAbstract" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="LiabilitiesAndStockholdersEquity" xlink:title="definition: StatementLineItems to LiabilitiesAndStockholdersEquity" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockValue" xlink:label="CommonStockValue" xlink:title="CommonStockValue" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CommonStockValue" xlink:title="definition: StatementLineItems to CommonStockValue" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="AdditionalPaidInCapitalCommonStock" xlink:title="AdditionalPaidInCapitalCommonStock" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AdditionalPaidInCapitalCommonStock" xlink:title="definition: StatementLineItems to AdditionalPaidInCapitalCommonStock" order="12.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:title="AccumulatedOtherComprehensiveIncomeLossNetOfTax" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:title="definition: StatementLineItems to AccumulatedOtherComprehensiveIncomeLossNetOfTax" order="13.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="RetainedEarningsAccumulatedDeficit" xlink:title="RetainedEarningsAccumulatedDeficit" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="RetainedEarningsAccumulatedDeficit" xlink:title="definition: StatementLineItems to RetainedEarningsAccumulatedDeficit" order="14.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="StockholdersEquity" xlink:title="StockholdersEquity" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="StockholdersEquity" xlink:title="definition: StatementLineItems to StockholdersEquity" order="15.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="AccountsPayableCurrent" xlink:title="AccountsPayableCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AccountsPayableCurrent" xlink:title="definition: StatementLineItems to AccountsPayableCurrent" order="16.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="EmployeeRelatedLiabilitiesCurrent" xlink:title="EmployeeRelatedLiabilitiesCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="EmployeeRelatedLiabilitiesCurrent" xlink:title="definition: StatementLineItems to EmployeeRelatedLiabilitiesCurrent" order="17.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="AccruedLiabilitiesCurrent" xlink:title="AccruedLiabilitiesCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AccruedLiabilitiesCurrent" xlink:title="definition: StatementLineItems to AccruedLiabilitiesCurrent" order="18.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedIncomeTaxesCurrent" xlink:label="AccruedIncomeTaxesCurrent" xlink:title="AccruedIncomeTaxesCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AccruedIncomeTaxesCurrent" xlink:title="definition: StatementLineItems to AccruedIncomeTaxesCurrent" order="19.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LongTermObligationsExcludingConvertibleDebtCurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:title="definition: StatementLineItems to LongTermObligationsExcludingConvertibleDebtCurrent" order="20.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="ContractWithCustomerLiabilityCurrent" xlink:title="ContractWithCustomerLiabilityCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ContractWithCustomerLiabilityCurrent" xlink:title="definition: StatementLineItems to ContractWithCustomerLiabilityCurrent" order="21.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="LiabilitiesCurrent" xlink:title="definition: StatementLineItems to LiabilitiesCurrent" order="22.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrentAbstract" xlink:label="AssetsCurrentAbstract" xlink:title="AssetsCurrentAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AssetsCurrentAbstract" xlink:title="definition: StatementLineItems to AssetsCurrentAbstract" order="23.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="PropertyPlantAndEquipmentNet" xlink:title="PropertyPlantAndEquipmentNet" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="PropertyPlantAndEquipmentNet" xlink:title="definition: StatementLineItems to PropertyPlantAndEquipmentNet" order="24.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="FiniteLivedIntangibleAssetsNet" xlink:title="FiniteLivedIntangibleAssetsNet" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="FiniteLivedIntangibleAssetsNet" xlink:title="definition: StatementLineItems to FiniteLivedIntangibleAssetsNet" order="25.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="OtherAssetsNoncurrent" xlink:title="OtherAssetsNoncurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="OtherAssetsNoncurrent" xlink:title="definition: StatementLineItems to OtherAssetsNoncurrent" order="26.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Assets" xlink:label="Assets" xlink:title="Assets" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="Assets" xlink:title="definition: StatementLineItems to Assets" order="27.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="CashAndCashEquivalentsAtCarryingValue" xlink:title="CashAndCashEquivalentsAtCarryingValue" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CashAndCashEquivalentsAtCarryingValue" xlink:title="definition: StatementLineItems to CashAndCashEquivalentsAtCarryingValue" order="28.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:title="AvailableForSaleSecuritiesDebtSecuritiesCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:title="definition: StatementLineItems to AvailableForSaleSecuritiesDebtSecuritiesCurrent" order="29.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerAssetNetCurrent" xlink:label="ContractWithCustomerAssetNetCurrent" xlink:title="ContractWithCustomerAssetNetCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ContractWithCustomerAssetNetCurrent" xlink:title="definition: StatementLineItems to ContractWithCustomerAssetNetCurrent" order="30.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="InventoryNet" xlink:title="definition: StatementLineItems to InventoryNet" order="31.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsCurrent" xlink:label="OtherAssetsCurrent" xlink:title="OtherAssetsCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="OtherAssetsCurrent" xlink:title="definition: StatementLineItems to OtherAssetsCurrent" order="32.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="AssetsCurrent" xlink:title="AssetsCurrent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AssetsCurrent" xlink:title="definition: StatementLineItems to AssetsCurrent" order="33.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="StatementLineItems" xlink:to="StatementTable" xlink:title="definition: StatementLineItems to StatementTable" order="34.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="StatementTable" xlink:to="DebtInstrumentAxis" xlink:title="definition: StatementTable to DebtInstrumentAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain_2" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain_2" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="LiabilitiesAndStockholdersEquityAbstract" xlink:title="definition: StatementLineItems to LiabilitiesAndStockholdersEquityAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="definition: StatementLineItems to DebtInstrumentInterestRateStatedPercentage" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="StockholdersEquityAbstract" xlink:title="definition: StatementLineItems to StockholdersEquityAbstract" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare" xlink:label="CommonStockParOrStatedValuePerShare" xlink:title="CommonStockParOrStatedValuePerShare" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CommonStockParOrStatedValuePerShare" xlink:title="definition: StatementLineItems to CommonStockParOrStatedValuePerShare" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesAuthorized" xlink:label="CommonStockSharesAuthorized" xlink:title="CommonStockSharesAuthorized" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CommonStockSharesAuthorized" xlink:title="definition: StatementLineItems to CommonStockSharesAuthorized" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesIssued" xlink:label="CommonStockSharesIssued" xlink:title="CommonStockSharesIssued" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CommonStockSharesIssued" xlink:title="definition: StatementLineItems to CommonStockSharesIssued" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesOutstanding" xlink:label="CommonStockSharesOutstanding" xlink:title="CommonStockSharesOutstanding" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CommonStockSharesOutstanding" xlink:title="definition: StatementLineItems to CommonStockSharesOutstanding" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="StatementLineItems" xlink:to="StatementTable" xlink:title="definition: StatementLineItems to StatementTable" order="8.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="StatementTable" xlink:to="DebtInstrumentAxis" xlink:title="definition: StatementTable to DebtInstrumentAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain_2" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain_2" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenuesAbstract" xlink:label="RevenuesAbstract" xlink:title="RevenuesAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="RevenuesAbstract" xlink:title="definition: StatementLineItems to RevenuesAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CostsAndExpensesAbstract" xlink:title="definition: StatementLineItems to CostsAndExpensesAbstract" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="OperatingIncomeLoss" xlink:title="OperatingIncomeLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="OperatingIncomeLoss" xlink:title="definition: StatementLineItems to OperatingIncomeLoss" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NonoperatingIncomeExpenseAbstract" xlink:title="definition: StatementLineItems to NonoperatingIncomeExpenseAbstract" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:title="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:title="definition: StatementLineItems to IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="IncomeTaxExpenseBenefit" xlink:title="IncomeTaxExpenseBenefit" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncomeTaxExpenseBenefit" xlink:title="definition: StatementLineItems to IncomeTaxExpenseBenefit" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NetIncomeLoss" xlink:title="definition: StatementLineItems to NetIncomeLoss" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasic" xlink:label="EarningsPerShareBasic" xlink:title="EarningsPerShareBasic" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="EarningsPerShareBasic" xlink:title="definition: StatementLineItems to EarningsPerShareBasic" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareDiluted" xlink:label="EarningsPerShareDiluted" xlink:title="EarningsPerShareDiluted" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="EarningsPerShareDiluted" xlink:title="definition: StatementLineItems to EarningsPerShareDiluted" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="WeightedAverageNumberOfSharesOutstandingBasic" xlink:title="WeightedAverageNumberOfSharesOutstandingBasic" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="WeightedAverageNumberOfSharesOutstandingBasic" xlink:title="definition: StatementLineItems to WeightedAverageNumberOfSharesOutstandingBasic" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="WeightedAverageNumberOfDilutedSharesOutstanding" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="definition: StatementLineItems to WeightedAverageNumberOfDilutedSharesOutstanding" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="InvestmentIncomeNet" xlink:title="definition: StatementLineItems to InvestmentIncomeNet" order="12.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="InterestExpense" xlink:title="definition: StatementLineItems to InterestExpense" order="13.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnInvestments" xlink:label="GainLossOnInvestments" xlink:title="GainLossOnInvestments" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="GainLossOnInvestments" xlink:title="definition: StatementLineItems to GainLossOnInvestments" order="14.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="OtherNonoperatingIncomeExpense" xlink:title="OtherNonoperatingIncomeExpense" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="OtherNonoperatingIncomeExpense" xlink:title="definition: StatementLineItems to OtherNonoperatingIncomeExpense" order="15.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="CostOfGoodsAndServicesSold" xlink:title="CostOfGoodsAndServicesSold" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CostOfGoodsAndServicesSold" xlink:title="definition: StatementLineItems to CostOfGoodsAndServicesSold" order="16.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchDevelopmentAndPatentExpense" xlink:label="ResearchDevelopmentAndPatentExpense" xlink:title="ResearchDevelopmentAndPatentExpense" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="ResearchDevelopmentAndPatentExpense" xlink:title="definition: StatementLineItems to ResearchDevelopmentAndPatentExpense" order="17.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="SellingGeneralAndAdministrativeExpense" xlink:title="SellingGeneralAndAdministrativeExpense" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="SellingGeneralAndAdministrativeExpense" xlink:title="definition: StatementLineItems to SellingGeneralAndAdministrativeExpense" order="18.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="CostsAndExpenses" xlink:title="definition: StatementLineItems to CostsAndExpenses" order="19.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="definition: StatementLineItems to RevenueFromContractWithCustomerExcludingAssessedTax" order="20.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="StatementLineItems" xlink:to="StatementTable" xlink:title="definition: StatementLineItems to StatementTable" order="21.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="StatementTable" xlink:to="ProductOrServiceAxis" xlink:title="definition: StatementTable to ProductOrServiceAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ProductOrServiceAxis" xlink:to="ProductsAndServicesDomain" xlink:title="definition: ProductOrServiceAxis to ProductsAndServicesDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain_2" xlink:title="ProductsAndServicesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ProductOrServiceAxis" xlink:to="ProductsAndServicesDomain_2" xlink:title="definition: ProductOrServiceAxis to ProductsAndServicesDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="CommercialMember" xlink:title="definition: ProductsAndServicesDomain to CommercialMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchAndDevelopmentRevenueMember" xlink:label="ResearchAndDevelopmentRevenueMember" xlink:title="ResearchAndDevelopmentRevenueMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueMember" xlink:title="definition: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CollaborativeAgreementRevenueMember" xlink:label="CollaborativeAgreementRevenueMember" xlink:title="CollaborativeAgreementRevenueMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="CollaborativeAgreementRevenueMember" xlink:title="definition: ResearchAndDevelopmentRevenueMember to CollaborativeAgreementRevenueMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_EplontersenJointDevelopmentRevenueMember" xlink:label="EplontersenJointDevelopmentRevenueMember" xlink:title="EplontersenJointDevelopmentRevenueMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="EplontersenJointDevelopmentRevenueMember" xlink:title="definition: ResearchAndDevelopmentRevenueMember to EplontersenJointDevelopmentRevenueMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SpinrazaRoyaltiesMember" xlink:label="SpinrazaRoyaltiesMember" xlink:title="SpinrazaRoyaltiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CommercialMember" xlink:to="SpinrazaRoyaltiesMember" xlink:title="definition: CommercialMember to SpinrazaRoyaltiesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProductMember" xlink:label="ProductMember" xlink:title="ProductMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CommercialMember" xlink:to="ProductMember" xlink:title="definition: CommercialMember to ProductMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LicensingAndOtherRoyaltiesMember" xlink:label="LicensingAndOtherRoyaltiesMember" xlink:title="LicensingAndOtherRoyaltiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CommercialMember" xlink:to="LicensingAndOtherRoyaltiesMember" xlink:title="definition: CommercialMember to LicensingAndOtherRoyaltiesMember" order="3.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:label="IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="IncreaseDecreaseInStockholdersEquityRollForward" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="definition: StatementLineItems to IncreaseDecreaseInStockholdersEquityRollForward" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:label="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="definition: StatementLineItems to StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesIssued" xlink:label="SharesIssued" xlink:title="SharesIssued" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="SharesIssued" xlink:title="definition: StatementLineItems to SharesIssued" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="NetIncomeLoss" xlink:title="definition: StatementLineItems to NetIncomeLoss" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:label="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:title="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:title="definition: StatementLineItems to OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="definition: StatementLineItems to OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:label="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:title="StockIssuedDuringPeriodValueShareBasedCompensationGross" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:title="definition: StatementLineItems to StockIssuedDuringPeriodValueShareBasedCompensationGross" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="definition: StatementLineItems to StockIssuedDuringPeriodSharesShareBasedCompensation" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:title="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:title="definition: StatementLineItems to AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="definition: StatementLineItems to AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:label="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:title="SharesPaidForTaxWithholdingForShareBasedCompensation" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="StatementLineItems" xlink:to="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:title="definition: StatementLineItems to SharesPaidForTaxWithholdingForShareBasedCompensation" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="StatementLineItems" xlink:to="StatementTable" xlink:title="definition: StatementLineItems to StatementTable" order="12.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="StatementEquityComponentsAxis" xlink:title="StatementEquityComponentsAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="StatementTable" xlink:to="StatementEquityComponentsAxis" xlink:title="definition: StatementTable to StatementEquityComponentsAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="EquityComponentDomain" xlink:title="EquityComponentDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="StatementEquityComponentsAxis" xlink:to="EquityComponentDomain" xlink:title="definition: StatementEquityComponentsAxis to EquityComponentDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="EquityComponentDomain_2" xlink:title="EquityComponentDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="StatementEquityComponentsAxis" xlink:to="EquityComponentDomain_2" xlink:title="definition: StatementEquityComponentsAxis to EquityComponentDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember" xlink:label="CommonStockMember" xlink:title="CommonStockMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityComponentDomain" xlink:to="CommonStockMember" xlink:title="definition: EquityComponentDomain to CommonStockMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="AdditionalPaidInCapitalMember" xlink:title="AdditionalPaidInCapitalMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityComponentDomain" xlink:to="AdditionalPaidInCapitalMember" xlink:title="definition: EquityComponentDomain to AdditionalPaidInCapitalMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:label="AccumulatedOtherComprehensiveIncomeMember" xlink:title="AccumulatedOtherComprehensiveIncomeMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityComponentDomain" xlink:to="AccumulatedOtherComprehensiveIncomeMember" xlink:title="definition: EquityComponentDomain to AccumulatedOtherComprehensiveIncomeMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsMember" xlink:label="RetainedEarningsMember" xlink:title="RetainedEarningsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityComponentDomain" xlink:to="RetainedEarningsMember" xlink:title="definition: EquityComponentDomain to RetainedEarningsMember" order="4.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/BasisOfPresentation" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPolicies" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/Investments" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/FairValueMeasurements" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/IncomeTaxes" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreements" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/ConvertibleDebt" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/BasisOfPresentationPolicies" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesPolicies" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesTables" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsTables" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/FairValueMeasurementsTables" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsTables" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/ConvertibleDebtTables">
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleNotesDisclosureLineItems" xlink:label="ConvertibleNotesDisclosureLineItems" xlink:title="ConvertibleNotesDisclosureLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleDebtTableTextBlock" xlink:label="ConvertibleDebtTableTextBlock" xlink:title="ConvertibleDebtTableTextBlock" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ConvertibleDebtTableTextBlock" xlink:title="definition: ConvertibleNotesDisclosureLineItems to ConvertibleDebtTableTextBlock" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleNotesDisclosureTable" xlink:label="ConvertibleNotesDisclosureTable" xlink:title="ConvertibleNotesDisclosureTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ConvertibleNotesDisclosureTable" xlink:title="definition: ConvertibleNotesDisclosureLineItems to ConvertibleNotesDisclosureTable" order="2.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="DebtInstrumentAxis" xlink:title="definition: ConvertibleNotesDisclosureTable to DebtInstrumentAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain_2" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain_2" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="DisaggregationOfRevenueLineItems" xlink:title="DisaggregationOfRevenueLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerAbstract" xlink:label="RevenueFromContractWithCustomerAbstract" xlink:title="RevenueFromContractWithCustomerAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="RevenueFromContractWithCustomerAbstract" xlink:title="definition: DisaggregationOfRevenueLineItems to RevenueFromContractWithCustomerAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="definition: DisaggregationOfRevenueLineItems to RevenueFromContractWithCustomerExcludingAssessedTax" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_UpfrontPaymentReceived" xlink:label="UpfrontPaymentReceived" xlink:title="UpfrontPaymentReceived" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="UpfrontPaymentReceived" xlink:title="definition: DisaggregationOfRevenueLineItems to UpfrontPaymentReceived" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:label="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:title="RevenueFromContractWithCustomerTransactionPriceAdditions" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:title="definition: DisaggregationOfRevenueLineItems to RevenueFromContractWithCustomerTransactionPriceAdditions" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfTargetsAdvanced" xlink:label="NumberOfTargetsAdvanced" xlink:title="NumberOfTargetsAdvanced" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="NumberOfTargetsAdvanced" xlink:title="definition: DisaggregationOfRevenueLineItems to NumberOfTargetsAdvanced" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfAgreementsWithCollaborationPartner" xlink:label="NumberOfAgreementsWithCollaborationPartner" xlink:title="NumberOfAgreementsWithCollaborationPartner" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="NumberOfAgreementsWithCollaborationPartner" xlink:title="definition: DisaggregationOfRevenueLineItems to NumberOfAgreementsWithCollaborationPartner" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfMaterialComponents" xlink:label="NumberOfMaterialComponents" xlink:title="NumberOfMaterialComponents" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="NumberOfMaterialComponents" xlink:title="definition: DisaggregationOfRevenueLineItems to NumberOfMaterialComponents" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:label="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:title="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:title="definition: DisaggregationOfRevenueLineItems to RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_RevenueFromContractWithCustomerTransactionPrice" xlink:label="RevenueFromContractWithCustomerTransactionPrice" xlink:title="RevenueFromContractWithCustomerTransactionPrice" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="RevenueFromContractWithCustomerTransactionPrice" xlink:title="definition: DisaggregationOfRevenueLineItems to RevenueFromContractWithCustomerTransactionPrice" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:label="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:title="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:title="definition: DisaggregationOfRevenueLineItems to PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="DisaggregationOfRevenueTable" xlink:title="DisaggregationOfRevenueTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="DisaggregationOfRevenueTable" xlink:title="definition: DisaggregationOfRevenueLineItems to DisaggregationOfRevenueTable" order="11.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="DisaggregationOfRevenueTable" xlink:to="TypeOfArrangementAxis" xlink:title="definition: DisaggregationOfRevenueTable to TypeOfArrangementAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="TypeOfArrangementAxis" xlink:to="ArrangementsAndNonarrangementTransactionsMember" xlink:title="definition: TypeOfArrangementAxis to ArrangementsAndNonarrangementTransactionsMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember_2" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="TypeOfArrangementAxis" xlink:to="ArrangementsAndNonarrangementTransactionsMember_2" xlink:title="definition: TypeOfArrangementAxis to ArrangementsAndNonarrangementTransactionsMember_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:label="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="BiogenCollaboration2013StrategicNeurologyMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to BiogenCollaboration2013StrategicNeurologyMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:label="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:title="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AlnylamCollaborationMember" xlink:label="AlnylamCollaborationMember" xlink:title="AlnylamCollaborationMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="AlnylamCollaborationMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to AlnylamCollaborationMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:label="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:title="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaboration2018StrategicNeurologyMember" xlink:label="BiogenCollaboration2018StrategicNeurologyMember" xlink:title="BiogenCollaboration2018StrategicNeurologyMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="BiogenCollaboration2018StrategicNeurologyMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to BiogenCollaboration2018StrategicNeurologyMember" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AstrazenecaCollaborationEplontersenMember" xlink:label="AstrazenecaCollaborationEplontersenMember" xlink:title="AstrazenecaCollaborationEplontersenMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="AstrazenecaCollaborationEplontersenMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to AstrazenecaCollaborationEplontersenMember" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="DisaggregationOfRevenueTable" xlink:to="ProductOrServiceAxis" xlink:title="definition: DisaggregationOfRevenueTable to ProductOrServiceAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ProductOrServiceAxis" xlink:to="ProductsAndServicesDomain" xlink:title="definition: ProductOrServiceAxis to ProductsAndServicesDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain_2" xlink:title="ProductsAndServicesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ProductOrServiceAxis" xlink:to="ProductsAndServicesDomain_2" xlink:title="definition: ProductOrServiceAxis to ProductsAndServicesDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_Ion859Member" xlink:label="Ion859Member" xlink:title="Ion859Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="Ion859Member" xlink:title="definition: ProductsAndServicesDomain to Ion859Member" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_Ion306Member" xlink:label="Ion306Member" xlink:title="Ion306Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="Ion306Member" xlink:title="definition: ProductsAndServicesDomain to Ion306Member" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="DisaggregationOfRevenueTable" xlink:to="MajorCustomersAxis" xlink:title="definition: DisaggregationOfRevenueTable to MajorCustomersAxis" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="MajorCustomersAxis" xlink:to="NameOfMajorCustomerDomain" xlink:title="definition: MajorCustomersAxis to NameOfMajorCustomerDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain_2" xlink:title="NameOfMajorCustomerDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="MajorCustomersAxis" xlink:to="NameOfMajorCustomerDomain_2" xlink:title="definition: MajorCustomersAxis to NameOfMajorCustomerDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenIncMember" xlink:label="BiogenIncMember" xlink:title="BiogenIncMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="NameOfMajorCustomerDomain" xlink:to="BiogenIncMember" xlink:title="definition: NameOfMajorCustomerDomain to BiogenIncMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EntityWideRevenueMajorCustomerLineItems" xlink:label="EntityWideRevenueMajorCustomerLineItems" xlink:title="EntityWideRevenueMajorCustomerLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SignificantPartnersAbstract" xlink:label="SignificantPartnersAbstract" xlink:title="SignificantPartnersAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EntityWideRevenueMajorCustomerLineItems" xlink:to="SignificantPartnersAbstract" xlink:title="definition: EntityWideRevenueMajorCustomerLineItems to SignificantPartnersAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EntityWideRevenueMajorCustomerLineItems" xlink:to="ConcentrationRiskPercentage1" xlink:title="definition: EntityWideRevenueMajorCustomerLineItems to ConcentrationRiskPercentage1" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfSignificantCustomers" xlink:label="NumberOfSignificantCustomers" xlink:title="NumberOfSignificantCustomers" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EntityWideRevenueMajorCustomerLineItems" xlink:to="NumberOfSignificantCustomers" xlink:title="definition: EntityWideRevenueMajorCustomerLineItems to NumberOfSignificantCustomers" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:label="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:title="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="EntityWideRevenueMajorCustomerLineItems" xlink:to="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:title="definition: EntityWideRevenueMajorCustomerLineItems to ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" order="4.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:to="ConcentrationRiskByBenchmarkAxis" xlink:title="definition: ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable to ConcentrationRiskByBenchmarkAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConcentrationRiskByBenchmarkAxis" xlink:to="ConcentrationRiskBenchmarkDomain" xlink:title="definition: ConcentrationRiskByBenchmarkAxis to ConcentrationRiskBenchmarkDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain_2" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConcentrationRiskByBenchmarkAxis" xlink:to="ConcentrationRiskBenchmarkDomain_2" xlink:title="definition: ConcentrationRiskByBenchmarkAxis to ConcentrationRiskBenchmarkDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableMember" xlink:label="AccountsReceivableMember" xlink:title="AccountsReceivableMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConcentrationRiskBenchmarkDomain" xlink:to="AccountsReceivableMember" xlink:title="definition: ConcentrationRiskBenchmarkDomain to AccountsReceivableMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:to="ConcentrationRiskByTypeAxis" xlink:title="definition: ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable to ConcentrationRiskByTypeAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConcentrationRiskByTypeAxis" xlink:to="ConcentrationRiskTypeDomain" xlink:title="definition: ConcentrationRiskByTypeAxis to ConcentrationRiskTypeDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain_2" xlink:title="ConcentrationRiskTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConcentrationRiskByTypeAxis" xlink:to="ConcentrationRiskTypeDomain_2" xlink:title="definition: ConcentrationRiskByTypeAxis to ConcentrationRiskTypeDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CreditConcentrationRiskMember" xlink:label="CreditConcentrationRiskMember" xlink:title="CreditConcentrationRiskMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConcentrationRiskTypeDomain" xlink:to="CreditConcentrationRiskMember" xlink:title="definition: ConcentrationRiskTypeDomain to CreditConcentrationRiskMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:to="MajorCustomersAxis" xlink:title="definition: ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable to MajorCustomersAxis" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="MajorCustomersAxis" xlink:to="NameOfMajorCustomerDomain" xlink:title="definition: MajorCustomersAxis to NameOfMajorCustomerDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain_2" xlink:title="NameOfMajorCustomerDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="MajorCustomersAxis" xlink:to="NameOfMajorCustomerDomain_2" xlink:title="definition: MajorCustomersAxis to NameOfMajorCustomerDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_TwoSignificantCustomersMember" xlink:label="TwoSignificantCustomersMember" xlink:title="TwoSignificantCustomersMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="NameOfMajorCustomerDomain" xlink:to="TwoSignificantCustomersMember" xlink:title="definition: NameOfMajorCustomerDomain to TwoSignificantCustomersMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesDeferredRevenueDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:label="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:title="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:label="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:title="CashCashEquivalentsAndShortTermInvestmentsAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:to="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:title="definition: ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems to CashCashEquivalentsAndShortTermInvestmentsAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:to="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="definition: ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems to NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:to="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="definition: ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems to NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:label="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:title="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:to="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:title="definition: ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems to NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnInvestments" xlink:label="GainLossOnInvestments" xlink:title="GainLossOnInvestments" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:to="GainLossOnInvestments" xlink:title="definition: ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems to GainLossOnInvestments" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:label="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:title="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:to="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:title="definition: ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems to ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" order="6.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:to="FinancialInstrumentAxis" xlink:title="definition: ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable to FinancialInstrumentAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="definition: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" xlink:title="definition: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:label="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:title="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:title="definition: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryLineItems" xlink:label="InventoryLineItems" xlink:title="InventoryLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNetAbstract" xlink:label="InventoryNetAbstract" xlink:title="InventoryNetAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InventoryLineItems" xlink:to="InventoryNetAbstract" xlink:title="definition: InventoryLineItems to InventoryNetAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryRawMaterials" xlink:label="InventoryRawMaterials" xlink:title="InventoryRawMaterials" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InventoryLineItems" xlink:to="InventoryRawMaterials" xlink:title="definition: InventoryLineItems to InventoryRawMaterials" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InventoryLineItems" xlink:to="InventoryWorkInProcess" xlink:title="definition: InventoryLineItems to InventoryWorkInProcess" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryFinishedGoods" xlink:label="InventoryFinishedGoods" xlink:title="InventoryFinishedGoods" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InventoryLineItems" xlink:to="InventoryFinishedGoods" xlink:title="definition: InventoryLineItems to InventoryFinishedGoods" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InventoryLineItems" xlink:to="InventoryNet" xlink:title="definition: InventoryLineItems to InventoryNet" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryCurrentTable" xlink:label="InventoryCurrentTable" xlink:title="InventoryCurrentTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="InventoryLineItems" xlink:to="InventoryCurrentTable" xlink:title="definition: InventoryLineItems to InventoryCurrentTable" order="6.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryAxis" xlink:label="PublicUtilitiesInventoryAxis" xlink:title="PublicUtilitiesInventoryAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="InventoryCurrentTable" xlink:to="PublicUtilitiesInventoryAxis" xlink:title="definition: InventoryCurrentTable to PublicUtilitiesInventoryAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryTypeDomain" xlink:label="PublicUtilitiesInventoryTypeDomain" xlink:title="PublicUtilitiesInventoryTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="PublicUtilitiesInventoryAxis" xlink:to="PublicUtilitiesInventoryTypeDomain" xlink:title="definition: PublicUtilitiesInventoryAxis to PublicUtilitiesInventoryTypeDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryTypeDomain" xlink:label="PublicUtilitiesInventoryTypeDomain_2" xlink:title="PublicUtilitiesInventoryTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="PublicUtilitiesInventoryAxis" xlink:to="PublicUtilitiesInventoryTypeDomain_2" xlink:title="definition: PublicUtilitiesInventoryAxis to PublicUtilitiesInventoryTypeDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ClinicalRawMaterialsMember" xlink:label="ClinicalRawMaterialsMember" xlink:title="ClinicalRawMaterialsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="PublicUtilitiesInventoryTypeDomain" xlink:to="ClinicalRawMaterialsMember" xlink:title="definition: PublicUtilitiesInventoryTypeDomain to ClinicalRawMaterialsMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CommercialRawMaterialsMember" xlink:label="CommercialRawMaterialsMember" xlink:title="CommercialRawMaterialsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="PublicUtilitiesInventoryTypeDomain" xlink:to="CommercialRawMaterialsMember" xlink:title="definition: PublicUtilitiesInventoryTypeDomain to CommercialRawMaterialsMember" order="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="LesseeLeaseDescriptionLineItems" xlink:title="LesseeLeaseDescriptionLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeDisclosureAbstract" xlink:label="LesseeDisclosureAbstract" xlink:title="LesseeDisclosureAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeDisclosureAbstract" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeDisclosureAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LesseeOperatingLeaseFreeRentPeriod" xlink:label="LesseeOperatingLeaseFreeRentPeriod" xlink:title="LesseeOperatingLeaseFreeRentPeriod" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseFreeRentPeriod" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseFreeRentPeriod" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDue" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeOperatingLeaseLiabilityPaymentsDue" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="LesseeLeaseDescriptionTable" xlink:title="LesseeLeaseDescriptionTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeLeaseDescriptionTable" xlink:title="definition: LesseeLeaseDescriptionLineItems to LesseeLeaseDescriptionTable" order="4.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="PropertyPlantAndEquipmentByTypeAxis" xlink:title="PropertyPlantAndEquipmentByTypeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="LesseeLeaseDescriptionTable" xlink:to="PropertyPlantAndEquipmentByTypeAxis" xlink:title="definition: LesseeLeaseDescriptionTable to PropertyPlantAndEquipmentByTypeAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="PropertyPlantAndEquipmentTypeDomain" xlink:title="PropertyPlantAndEquipmentTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="PropertyPlantAndEquipmentByTypeAxis" xlink:to="PropertyPlantAndEquipmentTypeDomain" xlink:title="definition: PropertyPlantAndEquipmentByTypeAxis to PropertyPlantAndEquipmentTypeDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="PropertyPlantAndEquipmentTypeDomain_2" xlink:title="PropertyPlantAndEquipmentTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="PropertyPlantAndEquipmentByTypeAxis" xlink:to="PropertyPlantAndEquipmentTypeDomain_2" xlink:title="definition: PropertyPlantAndEquipmentByTypeAxis to PropertyPlantAndEquipmentTypeDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BuildingMember" xlink:label="BuildingMember" xlink:title="BuildingMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="PropertyPlantAndEquipmentTypeDomain" xlink:to="BuildingMember" xlink:title="definition: PropertyPlantAndEquipmentTypeDomain to BuildingMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasicLineItems" xlink:label="EarningsPerShareBasicLineItems" xlink:title="EarningsPerShareBasicLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasicAbstract" xlink:label="EarningsPerShareBasicAbstract" xlink:title="EarningsPerShareBasicAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EarningsPerShareBasicLineItems" xlink:to="EarningsPerShareBasicAbstract" xlink:title="definition: EarningsPerShareBasicLineItems to EarningsPerShareBasicAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasic" xlink:label="EarningsPerShareBasic" xlink:title="EarningsPerShareBasic" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EarningsPerShareBasicLineItems" xlink:to="EarningsPerShareBasic" xlink:title="definition: EarningsPerShareBasicLineItems to EarningsPerShareBasic" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EarningsPerShareBasicLineItems" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="definition: EarningsPerShareBasicLineItems to DebtInstrumentInterestRateStatedPercentage" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:label="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:title="ScheduleOfEarningsPerShareBasicByCommonClassTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="EarningsPerShareBasicLineItems" xlink:to="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:title="definition: EarningsPerShareBasicLineItems to ScheduleOfEarningsPerShareBasicByCommonClassTable" order="4.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="DebtInstrumentAxis" xlink:title="definition: ScheduleOfEarningsPerShareBasicByCommonClassTable to DebtInstrumentAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain_2" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain_2" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes1PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes1PercentMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="3.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="DebtInstrumentLineItems" xlink:title="DebtInstrumentLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:label="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:title="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:title="definition: DebtInstrumentLineItems to LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentInterestRateStatedPercentage" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="DebtInstrumentInterestRateEffectivePercentage" xlink:title="DebtInstrumentInterestRateEffectivePercentage" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentInterestRateEffectivePercentage" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentInterestRateEffectivePercentage" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentTable" xlink:label="DebtInstrumentTable" xlink:title="DebtInstrumentTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentTable" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentTable" order="4.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="DebtInstrumentTable" xlink:to="DebtInstrumentAxis" xlink:title="definition: DebtInstrumentTable to DebtInstrumentAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain_2" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain_2" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesSegmentInformationDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAbstract" xlink:label="ShareBasedCompensationAbstract" xlink:title="ShareBasedCompensationAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="ShareBasedCompensationAbstract" xlink:title="definition: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to ShareBasedCompensationAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="AllocatedShareBasedCompensationExpense" xlink:title="AllocatedShareBasedCompensationExpense" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="AllocatedShareBasedCompensationExpense" xlink:title="definition: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to AllocatedShareBasedCompensationExpense" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:title="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:title="definition: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" order="3.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="IncomeStatementLocationAxis" xlink:title="IncomeStatementLocationAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="IncomeStatementLocationAxis" xlink:title="definition: ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable to IncomeStatementLocationAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="IncomeStatementLocationDomain" xlink:title="IncomeStatementLocationDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="IncomeStatementLocationAxis" xlink:to="IncomeStatementLocationDomain" xlink:title="definition: IncomeStatementLocationAxis to IncomeStatementLocationDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="IncomeStatementLocationDomain_2" xlink:title="IncomeStatementLocationDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="IncomeStatementLocationAxis" xlink:to="IncomeStatementLocationDomain_2" xlink:title="definition: IncomeStatementLocationAxis to IncomeStatementLocationDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfSalesMember" xlink:label="CostOfSalesMember" xlink:title="CostOfSalesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="IncomeStatementLocationDomain" xlink:to="CostOfSalesMember" xlink:title="definition: IncomeStatementLocationDomain to CostOfSalesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchDevelopmentAndPatentExpensesMember" xlink:label="ResearchDevelopmentAndPatentExpensesMember" xlink:title="ResearchDevelopmentAndPatentExpensesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="IncomeStatementLocationDomain" xlink:to="ResearchDevelopmentAndPatentExpensesMember" xlink:title="definition: IncomeStatementLocationDomain to ResearchDevelopmentAndPatentExpensesMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="SellingGeneralAndAdministrativeExpensesMember" xlink:title="SellingGeneralAndAdministrativeExpensesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="IncomeStatementLocationDomain" xlink:to="SellingGeneralAndAdministrativeExpensesMember" xlink:title="definition: IncomeStatementLocationDomain to SellingGeneralAndAdministrativeExpensesMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" order="12.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" order="13.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" order="14.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" order="15.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" order="16.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" order="17.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:title="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:title="definition: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" order="18.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="AwardTypeAxis" xlink:title="AwardTypeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="AwardTypeAxis" xlink:title="definition: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to AwardTypeAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:title="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="AwardTypeAxis" xlink:to="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:title="definition: AwardTypeAxis to ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2" xlink:title="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="AwardTypeAxis" xlink:to="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2" xlink:title="definition: AwardTypeAxis to ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="EmployeeStockOptionMember" xlink:title="EmployeeStockOptionMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="EmployeeStockOptionMember" xlink:title="definition: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to EmployeeStockOptionMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockMember" xlink:label="EmployeeStockMember" xlink:title="EmployeeStockMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="EmployeeStockMember" xlink:title="definition: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to EmployeeStockMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="RestrictedStockUnitsRSUMember" xlink:title="RestrictedStockUnitsRSUMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="RestrictedStockUnitsRSUMember" xlink:title="definition: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to RestrictedStockUnitsRSUMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PerformanceSharesMember" xlink:label="PerformanceSharesMember" xlink:title="PerformanceSharesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="PerformanceSharesMember" xlink:title="definition: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to PerformanceSharesMember" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:label="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:title="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EmployeeStockOptionMember" xlink:to="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:title="definition: EmployeeStockOptionMember to ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:label="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:title="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EmployeeStockOptionMember" xlink:to="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:title="definition: EmployeeStockOptionMember to ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GranteeStatusAxis" xlink:label="GranteeStatusAxis" xlink:title="GranteeStatusAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="GranteeStatusAxis" xlink:title="definition: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to GranteeStatusAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GranteeStatusDomain" xlink:label="GranteeStatusDomain" xlink:title="GranteeStatusDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="GranteeStatusAxis" xlink:to="GranteeStatusDomain" xlink:title="definition: GranteeStatusAxis to GranteeStatusDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GranteeStatusDomain" xlink:label="GranteeStatusDomain_2" xlink:title="GranteeStatusDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="GranteeStatusAxis" xlink:to="GranteeStatusDomain_2" xlink:title="definition: GranteeStatusAxis to GranteeStatusDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:label="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:title="ShareBasedPaymentArrangementBoardOfDirectorMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="GranteeStatusDomain" xlink:to="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:title="definition: GranteeStatusDomain to ShareBasedPaymentArrangementBoardOfDirectorMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedPaymentArrangementEmployeeMember" xlink:label="ShareBasedPaymentArrangementEmployeeMember" xlink:title="ShareBasedPaymentArrangementEmployeeMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="GranteeStatusDomain" xlink:to="ShareBasedPaymentArrangementEmployeeMember" xlink:title="definition: GranteeStatusDomain to ShareBasedPaymentArrangementEmployeeMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ExecutiveOfficerMember" xlink:label="ExecutiveOfficerMember" xlink:title="ExecutiveOfficerMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="GranteeStatusDomain" xlink:to="ExecutiveOfficerMember" xlink:title="definition: GranteeStatusDomain to ExecutiveOfficerMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingAxis" xlink:label="VestingAxis" xlink:title="VestingAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="VestingAxis" xlink:title="definition: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to VestingAxis" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingDomain" xlink:label="VestingDomain" xlink:title="VestingDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="VestingAxis" xlink:to="VestingDomain" xlink:title="definition: VestingAxis to VestingDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingDomain" xlink:label="VestingDomain_2" xlink:title="VestingDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="VestingAxis" xlink:to="VestingDomain_2" xlink:title="definition: VestingAxis to VestingDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheOneMember" xlink:label="ShareBasedCompensationAwardTrancheOneMember" xlink:title="ShareBasedCompensationAwardTrancheOneMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="VestingDomain" xlink:to="ShareBasedCompensationAwardTrancheOneMember" xlink:title="definition: VestingDomain to ShareBasedCompensationAwardTrancheOneMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheTwoMember" xlink:label="ShareBasedCompensationAwardTrancheTwoMember" xlink:title="ShareBasedCompensationAwardTrancheTwoMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="VestingDomain" xlink:to="ShareBasedCompensationAwardTrancheTwoMember" xlink:title="definition: VestingDomain to ShareBasedCompensationAwardTrancheTwoMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheThreeMember" xlink:label="ShareBasedCompensationAwardTrancheThreeMember" xlink:title="ShareBasedCompensationAwardTrancheThreeMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="VestingDomain" xlink:to="ShareBasedCompensationAwardTrancheThreeMember" xlink:title="definition: VestingDomain to ShareBasedCompensationAwardTrancheThreeMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="RangeAxis" xlink:title="definition: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to RangeAxis" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="RangeAxis" xlink:to="RangeMember" xlink:title="definition: RangeAxis to RangeMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="RangeMember_2" xlink:title="RangeMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="RangeAxis" xlink:to="RangeMember_2" xlink:title="definition: RangeAxis to RangeMember_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="MinimumMember" xlink:title="MinimumMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="RangeMember" xlink:to="MinimumMember" xlink:title="definition: RangeMember to MinimumMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="MaximumMember" xlink:title="MaximumMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="RangeMember" xlink:to="MaximumMember" xlink:title="definition: RangeMember to MaximumMember" order="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:label="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:title="AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleDebtSecuritiesAmortizedCostBasis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="AvailableForSaleSecuritiesDebtSecurities" xlink:title="AvailableForSaleSecuritiesDebtSecurities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesDebtSecurities" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesDebtSecurities" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiCost" xlink:label="EquitySecuritiesFvNiCost" xlink:title="EquitySecuritiesFvNiCost" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="EquitySecuritiesFvNiCost" xlink:title="definition: InvestmentHoldingsLineItems to EquitySecuritiesFvNiCost" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiUnrealizedGain" xlink:label="EquitySecuritiesFvNiUnrealizedGain" xlink:title="EquitySecuritiesFvNiUnrealizedGain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="EquitySecuritiesFvNiUnrealizedGain" xlink:title="definition: InvestmentHoldingsLineItems to EquitySecuritiesFvNiUnrealizedGain" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiUnrealizedLoss" xlink:label="EquitySecuritiesFvNiUnrealizedLoss" xlink:title="EquitySecuritiesFvNiUnrealizedLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="EquitySecuritiesFvNiUnrealizedLoss" xlink:title="definition: InvestmentHoldingsLineItems to EquitySecuritiesFvNiUnrealizedLoss" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNi" xlink:label="EquitySecuritiesFvNi" xlink:title="EquitySecuritiesFvNi" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="EquitySecuritiesFvNi" xlink:title="definition: InvestmentHoldingsLineItems to EquitySecuritiesFvNi" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" order="12.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" order="13.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:label="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:title="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:title="definition: InvestmentHoldingsLineItems to NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" order="14.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="InvestmentHoldingsLineItems" xlink:to="InvestmentHoldingsTable" xlink:title="definition: InvestmentHoldingsLineItems to InvestmentHoldingsTable" order="15.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="InvestmentHoldingsTable" xlink:to="FinancialInstrumentAxis" xlink:title="definition: InvestmentHoldingsTable to FinancialInstrumentAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="definition: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" xlink:title="definition: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="DebtSecuritiesMember" xlink:title="definition: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to DebtSecuritiesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesMember" xlink:label="EquitySecuritiesMember" xlink:title="EquitySecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="EquitySecuritiesMember" xlink:title="definition: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to EquitySecuritiesMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_EquitySecuritiesPubliclyTradedCompaniesMember" xlink:label="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:title="EquitySecuritiesPubliclyTradedCompaniesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquitySecuritiesMember" xlink:to="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:title="definition: EquitySecuritiesMember to EquitySecuritiesPubliclyTradedCompaniesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_EquitySecuritiesPrivateCompaniesMember" xlink:label="EquitySecuritiesPrivateCompaniesMember" xlink:title="EquitySecuritiesPrivateCompaniesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquitySecuritiesMember" xlink:to="EquitySecuritiesPrivateCompaniesMember" xlink:title="definition: EquitySecuritiesMember to EquitySecuritiesPrivateCompaniesMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="CorporateDebtSecuritiesMember" xlink:title="definition: DebtSecuritiesMember to CorporateDebtSecuritiesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember" xlink:label="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="USGovernmentAgenciesDebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="definition: DebtSecuritiesMember to USGovernmentAgenciesDebtSecuritiesMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember" xlink:label="USTreasurySecuritiesMember" xlink:title="USTreasurySecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="USTreasurySecuritiesMember" xlink:title="definition: DebtSecuritiesMember to USTreasurySecuritiesMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USStatesAndPoliticalSubdivisionsMember" xlink:label="USStatesAndPoliticalSubdivisionsMember" xlink:title="USStatesAndPoliticalSubdivisionsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="USStatesAndPoliticalSubdivisionsMember" xlink:title="definition: DebtSecuritiesMember to USStatesAndPoliticalSubdivisionsMember" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherDebtSecuritiesMember" xlink:label="OtherDebtSecuritiesMember" xlink:title="OtherDebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="OtherDebtSecuritiesMember" xlink:title="definition: DebtSecuritiesMember to OtherDebtSecuritiesMember" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentSecondaryCategorizationAxis" xlink:label="InvestmentSecondaryCategorizationAxis" xlink:title="InvestmentSecondaryCategorizationAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="InvestmentHoldingsTable" xlink:to="InvestmentSecondaryCategorizationAxis" xlink:title="definition: InvestmentHoldingsTable to InvestmentSecondaryCategorizationAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsBySecondaryCategorizationDomain" xlink:label="InvestmentsBySecondaryCategorizationDomain" xlink:title="InvestmentsBySecondaryCategorizationDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="InvestmentSecondaryCategorizationAxis" xlink:to="InvestmentsBySecondaryCategorizationDomain" xlink:title="definition: InvestmentSecondaryCategorizationAxis to InvestmentsBySecondaryCategorizationDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsBySecondaryCategorizationDomain" xlink:label="InvestmentsBySecondaryCategorizationDomain_2" xlink:title="InvestmentsBySecondaryCategorizationDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="InvestmentSecondaryCategorizationAxis" xlink:to="InvestmentsBySecondaryCategorizationDomain_2" xlink:title="definition: InvestmentSecondaryCategorizationAxis to InvestmentsBySecondaryCategorizationDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SecuritiesWithMaturityOfOneYearOrLessMember" xlink:label="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:title="SecuritiesWithMaturityOfOneYearOrLessMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentsBySecondaryCategorizationDomain" xlink:to="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:title="definition: InvestmentsBySecondaryCategorizationDomain to SecuritiesWithMaturityOfOneYearOrLessMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:label="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:title="SecuritiesWithMaturityOfMoreThanOneYearMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentsBySecondaryCategorizationDomain" xlink:to="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:title="definition: InvestmentsBySecondaryCategorizationDomain to SecuritiesWithMaturityOfMoreThanOneYearMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:label="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:title="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="InvestmentHoldingsTable" xlink:to="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:title="definition: InvestmentHoldingsTable to ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_EquityMethodInvesteeNameDomain" xlink:label="EquityMethodInvesteeNameDomain" xlink:title="EquityMethodInvesteeNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:to="EquityMethodInvesteeNameDomain" xlink:title="definition: ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis to EquityMethodInvesteeNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_EquityMethodInvesteeNameDomain" xlink:label="EquityMethodInvesteeNameDomain_2" xlink:title="EquityMethodInvesteeNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:to="EquityMethodInvesteeNameDomain_2" xlink:title="definition: ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis to EquityMethodInvesteeNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BicycleTherapeuticsPlcMember" xlink:label="BicycleTherapeuticsPlcMember" xlink:title="BicycleTherapeuticsPlcMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityMethodInvesteeNameDomain" xlink:to="BicycleTherapeuticsPlcMember" xlink:title="definition: EquityMethodInvesteeNameDomain to BicycleTherapeuticsPlcMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ProqrTherapeuticsNVMember" xlink:label="ProqrTherapeuticsNVMember" xlink:title="ProqrTherapeuticsNVMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityMethodInvesteeNameDomain" xlink:to="ProqrTherapeuticsNVMember" xlink:title="definition: EquityMethodInvesteeNameDomain to ProqrTherapeuticsNVMember" order="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAbstract" xlink:label="AvailableForSaleSecuritiesAbstract" xlink:title="AvailableForSaleSecuritiesAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesAbstract" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:title="definition: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:label="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:title="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="InvestmentHoldingsLineItems" xlink:to="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:title="definition: InvestmentHoldingsLineItems to DebtSecuritiesAvailableForSaleUnrealizedLossPosition" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="InvestmentHoldingsLineItems" xlink:to="InvestmentHoldingsTable" xlink:title="definition: InvestmentHoldingsLineItems to InvestmentHoldingsTable" order="11.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="InvestmentHoldingsTable" xlink:to="FinancialInstrumentAxis" xlink:title="definition: InvestmentHoldingsTable to FinancialInstrumentAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="definition: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" xlink:title="definition: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="DebtSecuritiesMember" xlink:title="definition: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to DebtSecuritiesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="CorporateDebtSecuritiesMember" xlink:title="definition: DebtSecuritiesMember to CorporateDebtSecuritiesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember" xlink:label="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="USGovernmentAgenciesDebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="definition: DebtSecuritiesMember to USGovernmentAgenciesDebtSecuritiesMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember" xlink:label="USTreasurySecuritiesMember" xlink:title="USTreasurySecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="USTreasurySecuritiesMember" xlink:title="definition: DebtSecuritiesMember to USTreasurySecuritiesMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USStatesAndPoliticalSubdivisionsMember" xlink:label="USStatesAndPoliticalSubdivisionsMember" xlink:title="USStatesAndPoliticalSubdivisionsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="USStatesAndPoliticalSubdivisionsMember" xlink:title="definition: DebtSecuritiesMember to USStatesAndPoliticalSubdivisionsMember" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherDebtSecuritiesMember" xlink:label="OtherDebtSecuritiesMember" xlink:title="OtherDebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtSecuritiesMember" xlink:to="OtherDebtSecuritiesMember" xlink:title="definition: DebtSecuritiesMember to OtherDebtSecuritiesMember" order="5.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/FairValueMeasurementsDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="FairValueNetAssetLiabilityAbstract" xlink:title="FairValueNetAssetLiabilityAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="FairValueNetAssetLiabilityAbstract" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to FairValueNetAssetLiabilityAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="CashAndCashEquivalentsFairValueDisclosure" xlink:title="CashAndCashEquivalentsFairValueDisclosure" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="CashAndCashEquivalentsFairValueDisclosure" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to CashAndCashEquivalentsFairValueDisclosure" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="AvailableForSaleSecuritiesDebtSecurities" xlink:title="AvailableForSaleSecuritiesDebtSecurities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="AvailableForSaleSecuritiesDebtSecurities" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to AvailableForSaleSecuritiesDebtSecurities" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNi" xlink:label="EquitySecuritiesFvNi" xlink:title="EquitySecuritiesFvNi" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="EquitySecuritiesFvNi" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to EquitySecuritiesFvNi" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="AssetsFairValueDisclosure" xlink:title="AssetsFairValueDisclosure" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="AssetsFairValueDisclosure" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to AssetsFairValueDisclosure" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to DebtInstrumentInterestRateStatedPercentage" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NotesPayableFairValueDisclosure" xlink:label="NotesPayableFairValueDisclosure" xlink:title="NotesPayableFairValueDisclosure" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="NotesPayableFairValueDisclosure" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to NotesPayableFairValueDisclosure" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" order="8.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="FairValueByMeasurementFrequencyAxis" xlink:title="FairValueByMeasurementFrequencyAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="FairValueByMeasurementFrequencyAxis" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to FairValueByMeasurementFrequencyAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="FairValueMeasurementFrequencyDomain" xlink:title="FairValueMeasurementFrequencyDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="FairValueByMeasurementFrequencyAxis" xlink:to="FairValueMeasurementFrequencyDomain" xlink:title="definition: FairValueByMeasurementFrequencyAxis to FairValueMeasurementFrequencyDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="FairValueMeasurementFrequencyDomain_2" xlink:title="FairValueMeasurementFrequencyDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="FairValueByMeasurementFrequencyAxis" xlink:to="FairValueMeasurementFrequencyDomain_2" xlink:title="definition: FairValueByMeasurementFrequencyAxis to FairValueMeasurementFrequencyDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsRecurringMember" xlink:label="FairValueMeasurementsRecurringMember" xlink:title="FairValueMeasurementsRecurringMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueMeasurementFrequencyDomain" xlink:to="FairValueMeasurementsRecurringMember" xlink:title="definition: FairValueMeasurementFrequencyDomain to FairValueMeasurementsRecurringMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="FairValueByFairValueHierarchyLevelAxis" xlink:title="FairValueByFairValueHierarchyLevelAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="FairValueByFairValueHierarchyLevelAxis" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to FairValueByFairValueHierarchyLevelAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="FairValueMeasurementsFairValueHierarchyDomain" xlink:title="FairValueMeasurementsFairValueHierarchyDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="FairValueByFairValueHierarchyLevelAxis" xlink:to="FairValueMeasurementsFairValueHierarchyDomain" xlink:title="definition: FairValueByFairValueHierarchyLevelAxis to FairValueMeasurementsFairValueHierarchyDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="FairValueMeasurementsFairValueHierarchyDomain_2" xlink:title="FairValueMeasurementsFairValueHierarchyDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="FairValueByFairValueHierarchyLevelAxis" xlink:to="FairValueMeasurementsFairValueHierarchyDomain_2" xlink:title="definition: FairValueByFairValueHierarchyLevelAxis to FairValueMeasurementsFairValueHierarchyDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel1Member" xlink:label="FairValueInputsLevel1Member" xlink:title="FairValueInputsLevel1Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueMeasurementsFairValueHierarchyDomain" xlink:to="FairValueInputsLevel1Member" xlink:title="definition: FairValueMeasurementsFairValueHierarchyDomain to FairValueInputsLevel1Member" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel2Member" xlink:label="FairValueInputsLevel2Member" xlink:title="FairValueInputsLevel2Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueMeasurementsFairValueHierarchyDomain" xlink:to="FairValueInputsLevel2Member" xlink:title="definition: FairValueMeasurementsFairValueHierarchyDomain to FairValueInputsLevel2Member" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="FairValueInputsLevel3Member" xlink:title="FairValueInputsLevel3Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="FairValueMeasurementsFairValueHierarchyDomain" xlink:to="FairValueInputsLevel3Member" xlink:title="definition: FairValueMeasurementsFairValueHierarchyDomain to FairValueInputsLevel3Member" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="FinancialInstrumentAxis" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to FinancialInstrumentAxis" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="definition: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" xlink:title="definition: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="CorporateDebtSecuritiesMember" xlink:title="definition: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to CorporateDebtSecuritiesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember" xlink:label="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="USGovernmentAgenciesDebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="definition: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to USGovernmentAgenciesDebtSecuritiesMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember" xlink:label="USTreasurySecuritiesMember" xlink:title="USTreasurySecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="USTreasurySecuritiesMember" xlink:title="definition: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to USTreasurySecuritiesMember" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USStatesAndPoliticalSubdivisionsMember" xlink:label="USStatesAndPoliticalSubdivisionsMember" xlink:title="USStatesAndPoliticalSubdivisionsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="USStatesAndPoliticalSubdivisionsMember" xlink:title="definition: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to USStatesAndPoliticalSubdivisionsMember" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherDebtSecuritiesMember" xlink:label="OtherDebtSecuritiesMember" xlink:title="OtherDebtSecuritiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="OtherDebtSecuritiesMember" xlink:title="definition: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to OtherDebtSecuritiesMember" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:label="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:title="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_EquityMethodInvesteeNameDomain" xlink:label="EquityMethodInvesteeNameDomain" xlink:title="EquityMethodInvesteeNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:to="EquityMethodInvesteeNameDomain" xlink:title="definition: ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis to EquityMethodInvesteeNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_EquityMethodInvesteeNameDomain" xlink:label="EquityMethodInvesteeNameDomain_2" xlink:title="EquityMethodInvesteeNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:to="EquityMethodInvesteeNameDomain_2" xlink:title="definition: ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis to EquityMethodInvesteeNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BicycleTherapeuticsPlcMember" xlink:label="BicycleTherapeuticsPlcMember" xlink:title="BicycleTherapeuticsPlcMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityMethodInvesteeNameDomain" xlink:to="BicycleTherapeuticsPlcMember" xlink:title="definition: EquityMethodInvesteeNameDomain to BicycleTherapeuticsPlcMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ProqrTherapeuticsNVMember" xlink:label="ProqrTherapeuticsNVMember" xlink:title="ProqrTherapeuticsNVMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="EquityMethodInvesteeNameDomain" xlink:to="ProqrTherapeuticsNVMember" xlink:title="definition: EquityMethodInvesteeNameDomain to ProqrTherapeuticsNVMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="BalanceSheetLocationAxis" xlink:title="BalanceSheetLocationAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="BalanceSheetLocationAxis" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to BalanceSheetLocationAxis" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="BalanceSheetLocationDomain" xlink:title="BalanceSheetLocationDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="BalanceSheetLocationAxis" xlink:to="BalanceSheetLocationDomain" xlink:title="definition: BalanceSheetLocationAxis to BalanceSheetLocationDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="BalanceSheetLocationDomain_2" xlink:title="BalanceSheetLocationDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="BalanceSheetLocationAxis" xlink:to="BalanceSheetLocationDomain_2" xlink:title="definition: BalanceSheetLocationAxis to BalanceSheetLocationDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsMember" xlink:label="CashAndCashEquivalentsMember" xlink:title="CashAndCashEquivalentsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="BalanceSheetLocationDomain" xlink:to="CashAndCashEquivalentsMember" xlink:title="definition: BalanceSheetLocationDomain to CashAndCashEquivalentsMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="DebtInstrumentAxis" xlink:title="definition: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to DebtInstrumentAxis" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain_2" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain_2" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="2.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/IncomeTaxesDetails" />
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to CollaborativeArrangementAndLicensingAgreementAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CumulativePaymentsReceived" xlink:label="CumulativePaymentsReceived" xlink:title="CumulativePaymentsReceived" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="CumulativePaymentsReceived" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to CumulativePaymentsReceived" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to RevenueFromContractWithCustomerExcludingAssessedTax" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ConcentrationRiskPercentage1" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to ConcentrationRiskPercentage1" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:label="ContractWithCustomerLiability" xlink:title="ContractWithCustomerLiability" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ContractWithCustomerLiability" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to ContractWithCustomerLiability" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfTargetsAdvanced" xlink:label="NumberOfTargetsAdvanced" xlink:title="NumberOfTargetsAdvanced" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NumberOfTargetsAdvanced" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NumberOfTargetsAdvanced" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NextPotentialPayment" xlink:label="NextPotentialPayment" xlink:title="NextPotentialPayment" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="NextPotentialPayment" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to NextPotentialPayment" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="definition: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="8.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="TypeOfArrangementAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to TypeOfArrangementAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="TypeOfArrangementAxis" xlink:to="ArrangementsAndNonarrangementTransactionsMember" xlink:title="definition: TypeOfArrangementAxis to ArrangementsAndNonarrangementTransactionsMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember_2" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="TypeOfArrangementAxis" xlink:to="ArrangementsAndNonarrangementTransactionsMember_2" xlink:title="definition: TypeOfArrangementAxis to ArrangementsAndNonarrangementTransactionsMember_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaborationsMember" xlink:label="BiogenCollaborationsMember" xlink:title="BiogenCollaborationsMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="BiogenCollaborationsMember" xlink:title="definition: ArrangementsAndNonarrangementTransactionsMember to BiogenCollaborationsMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:label="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="BiogenCollaboration2013StrategicNeurologyMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="BiogenCollaborationsMember" xlink:to="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="definition: BiogenCollaborationsMember to BiogenCollaboration2013StrategicNeurologyMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="RangeAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to RangeAxis" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="RangeAxis" xlink:to="RangeMember" xlink:title="definition: RangeAxis to RangeMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="RangeMember_2" xlink:title="RangeMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="RangeAxis" xlink:to="RangeMember_2" xlink:title="definition: RangeAxis to RangeMember_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="MaximumMember" xlink:title="MaximumMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="RangeMember" xlink:to="MaximumMember" xlink:title="definition: RangeMember to MaximumMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ProductOrServiceAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ProductOrServiceAxis" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ProductOrServiceAxis" xlink:to="ProductsAndServicesDomain" xlink:title="definition: ProductOrServiceAxis to ProductsAndServicesDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain_2" xlink:title="ProductsAndServicesDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ProductOrServiceAxis" xlink:to="ProductsAndServicesDomain_2" xlink:title="definition: ProductOrServiceAxis to ProductsAndServicesDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SpinrazaRoyaltiesMember" xlink:label="SpinrazaRoyaltiesMember" xlink:title="SpinrazaRoyaltiesMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="SpinrazaRoyaltiesMember" xlink:title="definition: ProductsAndServicesDomain to SpinrazaRoyaltiesMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchAndDevelopmentRevenueMember" xlink:label="ResearchAndDevelopmentRevenueMember" xlink:title="ResearchAndDevelopmentRevenueMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueMember" xlink:title="definition: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_Ion541Member" xlink:label="Ion541Member" xlink:title="Ion541Member" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ProductsAndServicesDomain" xlink:to="Ion541Member" xlink:title="definition: ProductsAndServicesDomain to Ion541Member" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ConcentrationRiskByBenchmarkAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ConcentrationRiskByBenchmarkAxis" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConcentrationRiskByBenchmarkAxis" xlink:to="ConcentrationRiskBenchmarkDomain" xlink:title="definition: ConcentrationRiskByBenchmarkAxis to ConcentrationRiskBenchmarkDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain_2" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConcentrationRiskByBenchmarkAxis" xlink:to="ConcentrationRiskBenchmarkDomain_2" xlink:title="definition: ConcentrationRiskByBenchmarkAxis to ConcentrationRiskBenchmarkDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerMember" xlink:label="RevenueFromContractWithCustomerMember" xlink:title="RevenueFromContractWithCustomerMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConcentrationRiskBenchmarkDomain" xlink:to="RevenueFromContractWithCustomerMember" xlink:title="definition: ConcentrationRiskBenchmarkDomain to RevenueFromContractWithCustomerMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ConcentrationRiskByTypeAxis" xlink:title="definition: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ConcentrationRiskByTypeAxis" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="ConcentrationRiskByTypeAxis" xlink:to="ConcentrationRiskTypeDomain" xlink:title="definition: ConcentrationRiskByTypeAxis to ConcentrationRiskTypeDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain_2" xlink:title="ConcentrationRiskTypeDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="ConcentrationRiskByTypeAxis" xlink:to="ConcentrationRiskTypeDomain_2" xlink:title="definition: ConcentrationRiskByTypeAxis to ConcentrationRiskTypeDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="CustomerConcentrationRiskMember" xlink:title="CustomerConcentrationRiskMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="ConcentrationRiskTypeDomain" xlink:to="CustomerConcentrationRiskMember" xlink:title="definition: ConcentrationRiskTypeDomain to CustomerConcentrationRiskMember" order="1.0" />
  </link:definitionLink>
  <link:definitionLink xlink:type="extended" xlink:role="http://ionispharma.com/role/ConvertibleDebtDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="DebtInstrumentLineItems" xlink:title="DebtInstrumentLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:label="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:title="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:title="definition: DebtInstrumentLineItems to ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="DebtInstrumentFaceAmount" xlink:title="DebtInstrumentFaceAmount" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentFaceAmount" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentFaceAmount" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentRepurchasedFaceAmount" xlink:label="DebtInstrumentRepurchasedFaceAmount" xlink:title="DebtInstrumentRepurchasedFaceAmount" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentRepurchasedFaceAmount" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentRepurchasedFaceAmount" order="3.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfConvertibleDebt" xlink:label="RepaymentsOfConvertibleDebt" xlink:title="RepaymentsOfConvertibleDebt" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="RepaymentsOfConvertibleDebt" xlink:title="definition: DebtInstrumentLineItems to RepaymentsOfConvertibleDebt" order="4.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="DebtInstrumentCarryingAmount" xlink:title="DebtInstrumentCarryingAmount" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentCarryingAmount" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentCarryingAmount" order="5.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredFinanceCostsNet" xlink:label="DeferredFinanceCostsNet" xlink:title="DeferredFinanceCostsNet" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DeferredFinanceCostsNet" xlink:title="definition: DebtInstrumentLineItems to DeferredFinanceCostsNet" order="6.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentMaturityDate" xlink:label="DebtInstrumentMaturityDate" xlink:title="DebtInstrumentMaturityDate" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentMaturityDate" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentMaturityDate" order="7.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentInterestRateStatedPercentage" order="8.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="DebtInstrumentInterestRateEffectivePercentage" xlink:title="DebtInstrumentInterestRateEffectivePercentage" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentInterestRateEffectivePercentage" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentInterestRateEffectivePercentage" order="9.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:label="DebtInstrumentConvertibleConversionPrice1" xlink:title="DebtInstrumentConvertibleConversionPrice1" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentConvertibleConversionPrice1" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentConvertibleConversionPrice1" order="10.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:label="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentConvertibleConversionPriceIncludingCallSpread" order="11.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:label="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="DebtInstrumentConvertibleSharesSubjectToConversion" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentConvertibleSharesSubjectToConversion" order="12.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CallSpread" xlink:label="CallSpread" xlink:title="CallSpread" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="CallSpread" xlink:title="definition: DebtInstrumentLineItems to CallSpread" order="13.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForHedgeFinancingActivities" xlink:label="PaymentsForHedgeFinancingActivities" xlink:title="PaymentsForHedgeFinancingActivities" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="PaymentsForHedgeFinancingActivities" xlink:title="definition: DebtInstrumentLineItems to PaymentsForHedgeFinancingActivities" order="14.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfWarrants" xlink:label="ProceedsFromIssuanceOfWarrants" xlink:title="ProceedsFromIssuanceOfWarrants" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="ProceedsFromIssuanceOfWarrants" xlink:title="definition: DebtInstrumentLineItems to ProceedsFromIssuanceOfWarrants" order="15.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt" xlink:label="GainsLossesOnExtinguishmentOfDebt" xlink:title="GainsLossesOnExtinguishmentOfDebt" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="GainsLossesOnExtinguishmentOfDebt" xlink:title="definition: DebtInstrumentLineItems to GainsLossesOnExtinguishmentOfDebt" order="16.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:label="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" order="17.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentTable" xlink:label="DebtInstrumentTable" xlink:title="DebtInstrumentTable" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="DebtInstrumentLineItems" xlink:to="DebtInstrumentTable" xlink:title="definition: DebtInstrumentLineItems to DebtInstrumentTable" order="18.0" t1:closed="true" t1:contextElement="segment" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="DebtInstrumentTable" xlink:to="DebtInstrumentAxis" xlink:title="definition: DebtInstrumentTable to DebtInstrumentAxis" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain_2" xlink:title="DebtInstrumentNameDomain" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain_2" xlink:title="definition: DebtInstrumentAxis to DebtInstrumentNameDomain_2" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="1.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="2.0" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes1PercentMember" xlink:title="definition: DebtInstrumentNameDomain to ConvertibleSeniorNotes1PercentMember" order="3.0" />
  </link:definitionLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>9
<FILENAME>ions-20220331_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 8.0.0.0 Broadridge-->
<link:linkbase xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance">
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/netLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/net-2009-12-16.xsd#netLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedTotalLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedTotalLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedNetLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedNetLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedTerseLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedPeriodEndLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedPeriodEndLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedPeriodStartLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedPeriodStartLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedLabel" />
  <link:labelLink xlink:type="extended" xlink:role="http://www.xbrl.org/2003/role/link">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="AwardTypeAxis" xlink:title="AwardTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AwardTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AwardTypeAxis_lbl" xml:lang="en-US" id="us-gaap_AwardTypeAxis_lbl">Award Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AwardTypeAxis" xlink:to="us-gaap_AwardTypeAxis_lbl" xlink:title="label: AwardTypeAxis to us-gaap_AwardTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ArrangementsAndNonarrangementTransactionsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ArrangementsAndNonarrangementTransactionsMember_lbl" xml:lang="en-US" id="us-gaap_ArrangementsAndNonarrangementTransactionsMember_lbl">Arrangements and Non-arrangement Transactions [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="us-gaap_ArrangementsAndNonarrangementTransactionsMember_lbl" xlink:title="label: ArrangementsAndNonarrangementTransactionsMember to us-gaap_ArrangementsAndNonarrangementTransactionsMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccountingPoliciesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccountingPoliciesAbstract_lbl" xml:lang="en-US" id="us-gaap_AccountingPoliciesAbstract_lbl">Significant Accounting Policies [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountingPoliciesAbstract" xlink:to="us-gaap_AccountingPoliciesAbstract_lbl" xlink:title="label: AccountingPoliciesAbstract to us-gaap_AccountingPoliciesAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="AccountsPayableCurrent" xlink:title="AccountsPayableCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccountsPayableCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccountsPayableCurrent_lbl" xml:lang="en-US" id="us-gaap_AccountsPayableCurrent_lbl">Accounts payable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountsPayableCurrent" xlink:to="us-gaap_AccountsPayableCurrent_lbl" xlink:title="label: AccountsPayableCurrent to us-gaap_AccountsPayableCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccountsPayableCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccountsPayableCurrent_lbl1" xml:lang="en-US" id="us-gaap_AccountsPayableCurrent_lbl1">Accounts Payable, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountsPayableCurrent" xlink:to="us-gaap_AccountsPayableCurrent_lbl1" xlink:title="label: AccountsPayableCurrent to us-gaap_AccountsPayableCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableMember" xlink:label="AccountsReceivableMember" xlink:title="AccountsReceivableMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccountsReceivableMember_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_AccountsReceivableMember_lbl" xml:lang="en-US" id="us-gaap_AccountsReceivableMember_lbl">Contracts Receivables [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountsReceivableMember" xlink:to="us-gaap_AccountsReceivableMember_lbl" xlink:title="label: AccountsReceivableMember to us-gaap_AccountsReceivableMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccountsReceivableMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccountsReceivableMember_lbl1" xml:lang="en-US" id="us-gaap_AccountsReceivableMember_lbl1">Accounts Receivable [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccountsReceivableMember" xlink:to="us-gaap_AccountsReceivableMember_lbl1" xlink:title="label: AccountsReceivableMember to us-gaap_AccountsReceivableMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:label="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:title="AccretionAmortizationOfDiscountsAndPremiumsInvestments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl" xml:lang="en-US" id="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl">Amortization of premium on investments, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:to="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl" xlink:title="label: AccretionAmortizationOfDiscountsAndPremiumsInvestments to us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl1" xml:lang="en-US" id="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl1">Accretion (Amortization) of Discounts and Premiums, Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:to="us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl1" xlink:title="label: AccretionAmortizationOfDiscountsAndPremiumsInvestments to us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="AccruedLiabilitiesCurrent" xlink:title="AccruedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccruedLiabilitiesCurrent_lbl" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrent_lbl">Accrued liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedLiabilitiesCurrent_lbl" xlink:title="label: AccruedLiabilitiesCurrent to us-gaap_AccruedLiabilitiesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccruedLiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrent_lbl1">Accrued Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedLiabilitiesCurrent_lbl1" xlink:title="label: AccruedLiabilitiesCurrent to us-gaap_AccruedLiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedIncomeTaxesCurrent" xlink:label="AccruedIncomeTaxesCurrent" xlink:title="AccruedIncomeTaxesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedIncomeTaxesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccruedIncomeTaxesCurrent_lbl" xml:lang="en-US" id="us-gaap_AccruedIncomeTaxesCurrent_lbl">Income taxes payable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedIncomeTaxesCurrent" xlink:to="us-gaap_AccruedIncomeTaxesCurrent_lbl" xlink:title="label: AccruedIncomeTaxesCurrent to us-gaap_AccruedIncomeTaxesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedIncomeTaxesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccruedIncomeTaxesCurrent_lbl1" xml:lang="en-US" id="us-gaap_AccruedIncomeTaxesCurrent_lbl1">Accrued Income Taxes, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedIncomeTaxesCurrent" xlink:to="us-gaap_AccruedIncomeTaxesCurrent_lbl1" xlink:title="label: AccruedIncomeTaxesCurrent to us-gaap_AccruedIncomeTaxesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:title="AccumulatedOtherComprehensiveIncomeLossNetOfTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl" xml:lang="en-US" id="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl">Accumulated other comprehensive loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl" xlink:title="label: AccumulatedOtherComprehensiveIncomeLossNetOfTax to us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl1" xml:lang="en-US" id="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl1">Accumulated Other Comprehensive Income (Loss), Net of Tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl1" xlink:title="label: AccumulatedOtherComprehensiveIncomeLossNetOfTax to us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:label="AccumulatedOtherComprehensiveIncomeMember" xlink:title="AccumulatedOtherComprehensiveIncomeMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccumulatedOtherComprehensiveIncomeMember_lbl" xml:lang="en-US" id="us-gaap_AccumulatedOtherComprehensiveIncomeMember_lbl">Accumulated Other Comprehensive Loss [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccumulatedOtherComprehensiveIncomeMember" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeMember_lbl" xlink:title="label: AccumulatedOtherComprehensiveIncomeMember to us-gaap_AccumulatedOtherComprehensiveIncomeMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="AdditionalPaidInCapitalCommonStock" xlink:title="AdditionalPaidInCapitalCommonStock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AdditionalPaidInCapitalCommonStock_lbl" xml:lang="en-US" id="us-gaap_AdditionalPaidInCapitalCommonStock_lbl">Additional paid-in capital</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdditionalPaidInCapitalCommonStock" xlink:to="us-gaap_AdditionalPaidInCapitalCommonStock_lbl" xlink:title="label: AdditionalPaidInCapitalCommonStock to us-gaap_AdditionalPaidInCapitalCommonStock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" xml:lang="en-US" id="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1">Additional Paid in Capital, Common Stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdditionalPaidInCapitalCommonStock" xlink:to="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" xlink:title="label: AdditionalPaidInCapitalCommonStock to us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="AdditionalPaidInCapitalMember" xlink:title="AdditionalPaidInCapitalMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdditionalPaidInCapitalMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdditionalPaidInCapitalMember_lbl" xml:lang="en-US" id="us-gaap_AdditionalPaidInCapitalMember_lbl">Additional Paid In Capital [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdditionalPaidInCapitalMember" xlink:to="us-gaap_AdditionalPaidInCapitalMember_lbl" xlink:title="label: AdditionalPaidInCapitalMember to us-gaap_AdditionalPaidInCapitalMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:title="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl" xml:lang="en-US" id="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl">Stock-based compensation expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl" xlink:title="label: AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue to us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl1" xml:lang="en-US" id="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl1">APIC, Share-based Payment Arrangement, Increase for Cost Recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:to="us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl1" xlink:title="label: AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue to us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl">Adjustments to reconcile net loss to 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="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl" xlink:title="label: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" xlink:title="label: AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation to us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1">Share-based Payment Arrangement, Decrease for Tax Withholding Obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xlink:title="label: AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation to us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="AllocatedShareBasedCompensationExpense" xlink:title="AllocatedShareBasedCompensationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_AllocatedShareBasedCompensationExpense_lbl" xml:lang="en-US" id="us-gaap_AllocatedShareBasedCompensationExpense_lbl">Non-cash stock-based compensation expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllocatedShareBasedCompensationExpense" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense_lbl" xlink:title="label: AllocatedShareBasedCompensationExpense to us-gaap_AllocatedShareBasedCompensationExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xml:lang="en-US" id="us-gaap_AllocatedShareBasedCompensationExpense_lbl1">Share-based Payment Arrangement, Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllocatedShareBasedCompensationExpense" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xlink:title="label: AllocatedShareBasedCompensationExpense to us-gaap_AllocatedShareBasedCompensationExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:label="AmortizationOfIntangibleAssets" xlink:title="AmortizationOfIntangibleAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfIntangibleAssets_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AmortizationOfIntangibleAssets_lbl" xml:lang="en-US" id="us-gaap_AmortizationOfIntangibleAssets_lbl">Amortization of patents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfIntangibleAssets" xlink:to="us-gaap_AmortizationOfIntangibleAssets_lbl" xlink:title="label: AmortizationOfIntangibleAssets to us-gaap_AmortizationOfIntangibleAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfIntangibleAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfIntangibleAssets_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfIntangibleAssets_lbl1">Amortization of Intangible Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfIntangibleAssets" xlink:to="us-gaap_AmortizationOfIntangibleAssets_lbl1" xlink:title="label: AmortizationOfIntangibleAssets to us-gaap_AmortizationOfIntangibleAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfFinancingCosts" xlink:label="AmortizationOfFinancingCosts" xlink:title="AmortizationOfFinancingCosts" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfFinancingCosts_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AmortizationOfFinancingCosts_lbl" xml:lang="en-US" id="us-gaap_AmortizationOfFinancingCosts_lbl">Amortization of debt issuance costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfFinancingCosts" xlink:to="us-gaap_AmortizationOfFinancingCosts_lbl" xlink:title="label: AmortizationOfFinancingCosts to us-gaap_AmortizationOfFinancingCosts_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfFinancingCosts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfFinancingCosts_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfFinancingCosts_lbl1">Amortization of Debt Issuance Costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfFinancingCosts" xlink:to="us-gaap_AmortizationOfFinancingCosts_lbl1" xlink:title="label: AmortizationOfFinancingCosts to us-gaap_AmortizationOfFinancingCosts_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Assets" xlink:label="Assets" xlink:title="Assets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Assets_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_Assets_lbl" xml:lang="en-US" id="us-gaap_Assets_lbl">Total assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Assets" xlink:to="us-gaap_Assets_lbl" xlink:title="label: Assets to us-gaap_Assets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Assets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Assets_lbl1" xml:lang="en-US" id="us-gaap_Assets_lbl1">Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Assets" xlink:to="us-gaap_Assets_lbl1" xlink:title="label: Assets to us-gaap_Assets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsAbstract" xlink:label="AssetsAbstract" xlink:title="AssetsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AssetsAbstract_lbl" xml:lang="en-US" id="us-gaap_AssetsAbstract_lbl">ASSETS</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetsAbstract" xlink:to="us-gaap_AssetsAbstract_lbl" xlink:title="label: AssetsAbstract to us-gaap_AssetsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsAbstract_lbl1" xml:lang="en-US" id="us-gaap_AssetsAbstract_lbl1">Assets [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetsAbstract" xlink:to="us-gaap_AssetsAbstract_lbl1" xlink:title="label: AssetsAbstract to us-gaap_AssetsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="AssetsFairValueDisclosure" xlink:title="AssetsFairValueDisclosure" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsFairValueDisclosure_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_AssetsFairValueDisclosure_lbl" xml:lang="en-US" id="us-gaap_AssetsFairValueDisclosure_lbl">Total</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetsFairValueDisclosure" xlink:to="us-gaap_AssetsFairValueDisclosure_lbl" xlink:title="label: AssetsFairValueDisclosure to us-gaap_AssetsFairValueDisclosure_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsFairValueDisclosure_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsFairValueDisclosure_lbl1" xml:lang="en-US" id="us-gaap_AssetsFairValueDisclosure_lbl1">Assets, Fair Value Disclosure</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetsFairValueDisclosure" xlink:to="us-gaap_AssetsFairValueDisclosure_lbl1" xlink:title="label: AssetsFairValueDisclosure to us-gaap_AssetsFairValueDisclosure_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="AssetsCurrent" xlink:title="AssetsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_AssetsCurrent_lbl" xml:lang="en-US" id="us-gaap_AssetsCurrent_lbl">Total current assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetsCurrent" xlink:to="us-gaap_AssetsCurrent_lbl" xlink:title="label: AssetsCurrent to us-gaap_AssetsCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsCurrent_lbl1" xml:lang="en-US" id="us-gaap_AssetsCurrent_lbl1">Assets, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetsCurrent" xlink:to="us-gaap_AssetsCurrent_lbl1" xlink:title="label: AssetsCurrent to us-gaap_AssetsCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrentAbstract" xlink:label="AssetsCurrentAbstract" xlink:title="AssetsCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AssetsCurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_AssetsCurrentAbstract_lbl">Current assets:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetsCurrentAbstract" xlink:to="us-gaap_AssetsCurrentAbstract_lbl" xlink:title="label: AssetsCurrentAbstract to us-gaap_AssetsCurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_AssetsCurrentAbstract_lbl1">Assets, Current [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetsCurrentAbstract" xlink:to="us-gaap_AssetsCurrentAbstract_lbl1" xlink:title="label: AssetsCurrentAbstract to us-gaap_AssetsCurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl">Unrealized Losses [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1">Debt Securities, Available-for-sale, Unrealized Loss Position, Accumulated Loss [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl">Gross unrealized losses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl" xlink:title="label: AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax to us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1">Debt Securities, Available-for-sale, Accumulated Gross Unrealized Loss, before Tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1" xlink:title="label: AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax to us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:label="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl">Summary of Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl" xlink:title="label: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl">Gross unrealized gains</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl" xlink:title="label: AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax to us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl1">Debt Securities, Available-for-sale, Accumulated Gross Unrealized Gain, before Tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl1" xlink:title="label: AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax to us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:title="AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl">Amortized cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl" xlink:title="label: AvailableForSaleDebtSecuritiesAmortizedCostBasis to us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl1">Debt Securities, Available-for-sale, Amortized Cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl1" xlink:title="label: AvailableForSaleDebtSecuritiesAmortizedCostBasis to us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl">Contract Maturity of Available-for-Sale Securities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAbstract to us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl1">Available-for-sale Securities, Debt Maturities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAbstract to us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAbstract" xlink:label="AvailableForSaleSecuritiesAbstract" xlink:title="AvailableForSaleSecuritiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesAbstract_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesAbstract_lbl">Temporarily Impaired Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesAbstract_lbl" xlink:title="label: AvailableForSaleSecuritiesAbstract to us-gaap_AvailableForSaleSecuritiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesAbstract_lbl1">Debt Securities, Available-for-sale [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesAbstract_lbl1" xlink:title="label: AvailableForSaleSecuritiesAbstract to us-gaap_AvailableForSaleSecuritiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl">Estimated Fair Value [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl1">Available-for-sale Securities, Continuous Unrealized Loss Position, Qualitative Disclosure [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl1" xlink:title="label: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract to us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="AvailableForSaleSecuritiesDebtSecurities" xlink:title="AvailableForSaleSecuritiesDebtSecurities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl">Estimated fair value</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtSecurities" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtSecurities to us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl1">Available-for-sale securities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtSecurities" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtSecurities to us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl2" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl2">Debt Securities, Available-for-sale</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtSecurities" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtSecurities to us-gaap_AvailableForSaleSecuritiesDebtSecurities_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:title="AvailableForSaleSecuritiesDebtSecuritiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl">Short-term investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtSecuritiesCurrent to us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl1">Debt Securities, Available-for-sale, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtSecuritiesCurrent to us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="BalanceSheetLocationDomain" xlink:title="BalanceSheetLocationDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_BalanceSheetLocationDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_BalanceSheetLocationDomain_lbl" xml:lang="en-US" id="us-gaap_BalanceSheetLocationDomain_lbl">Balance Sheet Location [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BalanceSheetLocationDomain" xlink:to="us-gaap_BalanceSheetLocationDomain_lbl" xlink:title="label: BalanceSheetLocationDomain to us-gaap_BalanceSheetLocationDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="BalanceSheetLocationAxis" xlink:title="BalanceSheetLocationAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_BalanceSheetLocationAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_BalanceSheetLocationAxis_lbl" xml:lang="en-US" id="us-gaap_BalanceSheetLocationAxis_lbl">Balance Sheet Location [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BalanceSheetLocationAxis" xlink:to="us-gaap_BalanceSheetLocationAxis_lbl" xlink:title="label: BalanceSheetLocationAxis to us-gaap_BalanceSheetLocationAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BasisOfAccountingPolicyPolicyTextBlock" xlink:label="BasisOfAccountingPolicyPolicyTextBlock" xlink:title="BasisOfAccountingPolicyPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_BasisOfAccountingPolicyPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_BasisOfAccountingPolicyPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_BasisOfAccountingPolicyPolicyTextBlock_lbl">Basis of Presentation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BasisOfAccountingPolicyPolicyTextBlock" xlink:to="us-gaap_BasisOfAccountingPolicyPolicyTextBlock_lbl" xlink:title="label: BasisOfAccountingPolicyPolicyTextBlock to us-gaap_BasisOfAccountingPolicyPolicyTextBlock_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BuildingMember" xlink:label="BuildingMember" xlink:title="BuildingMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_BuildingMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_BuildingMember_lbl" xml:lang="en-US" id="us-gaap_BuildingMember_lbl">Office Space in Boston, Massachusetts [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BuildingMember" xlink:to="us-gaap_BuildingMember_lbl" xlink:title="label: BuildingMember to us-gaap_BuildingMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_BuildingMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_BuildingMember_lbl1" xml:lang="en-US" id="us-gaap_BuildingMember_lbl1">Building [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BuildingMember" xlink:to="us-gaap_BuildingMember_lbl1" xlink:title="label: BuildingMember to us-gaap_BuildingMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl" xml:lang="en-US" id="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl">Net (decrease) increase in cash and cash equivalents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl" xlink:title="label: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect to us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl1" xml:lang="en-US" id="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl1">Cash, Cash Equivalents, Restricted Cash and Restricted Cash Equivalents, Period Increase (Decrease), Including Exchange Rate Effect</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:to="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl1" xlink:title="label: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect to us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="CashAndCashEquivalentsFairValueDisclosure" xlink:title="CashAndCashEquivalentsFairValueDisclosure" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl">Cash equivalents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashAndCashEquivalentsFairValueDisclosure" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl" xlink:title="label: CashAndCashEquivalentsFairValueDisclosure to us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl1" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl1">Cash and Cash Equivalents, Fair Value Disclosure</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashAndCashEquivalentsFairValueDisclosure" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl1" xlink:title="label: CashAndCashEquivalentsFairValueDisclosure to us-gaap_CashAndCashEquivalentsFairValueDisclosure_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl" xml:lang="en-US" id="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl">Cash and cash equivalents at end of period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl" xlink:title="label: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents to us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl1" xml:lang="en-US" id="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl1">Cash and cash equivalents at beginning of period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl1" xlink:title="label: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents to us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl2" xml:lang="en-US" id="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl2">Cash, Cash Equivalents, Restricted Cash and Restricted Cash Equivalents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl2" xlink:title="label: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents to us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsMember" xlink:label="CashAndCashEquivalentsMember" xlink:title="CashAndCashEquivalentsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashAndCashEquivalentsMember_lbl" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsMember_lbl">Cash and Cash Equivalents [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashAndCashEquivalentsMember" xlink:to="us-gaap_CashAndCashEquivalentsMember_lbl" xlink:title="label: CashAndCashEquivalentsMember to us-gaap_CashAndCashEquivalentsMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="CashAndCashEquivalentsAtCarryingValue" xlink:title="CashAndCashEquivalentsAtCarryingValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl">Cash and cash equivalents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashAndCashEquivalentsAtCarryingValue" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl" xlink:title="label: CashAndCashEquivalentsAtCarryingValue to us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1">Cash and Cash Equivalents, at Carrying Value</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashAndCashEquivalentsAtCarryingValue" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1" xlink:title="label: CashAndCashEquivalentsAtCarryingValue to us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:label="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:title="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl">Supplemental disclosures of non-cash investing and financing activities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:to="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl" xlink:title="label: CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract to us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl1" xml:lang="en-US" id="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl1">Cash Flow, Noncash Investing and Financing Activities Disclosure [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:to="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl1" xlink:title="label: CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract to us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:label="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:title="CashCashEquivalentsAndShortTermInvestmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl" xml:lang="en-US" id="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl">Cash, Cash Equivalents and Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:to="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl" xlink:title="label: CashCashEquivalentsAndShortTermInvestmentsAbstract to us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl1" xml:lang="en-US" id="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl1">Cash, Cash Equivalents, and Short-term Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:to="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl1" xlink:title="label: CashCashEquivalentsAndShortTermInvestmentsAbstract to us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementDisclosureTextBlock" xlink:label="CollaborativeArrangementDisclosureTextBlock" xlink:title="CollaborativeArrangementDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl">Collaborative Arrangements and Licensing Agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementDisclosureTextBlock" xlink:to="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" xlink:title="label: CollaborativeArrangementDisclosureTextBlock to us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1">Collaborative Arrangement Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementDisclosureTextBlock" xlink:to="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xlink:title="label: CollaborativeArrangementDisclosureTextBlock to us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_lbl" xml:lang="en-US" id="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_lbl">Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_lbl" xlink:title="label: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember" xlink:label="CommonStockMember" xlink:title="CommonStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockMember_lbl" xml:lang="en-US" id="us-gaap_CommonStockMember_lbl">Common Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockMember" xlink:to="us-gaap_CommonStockMember_lbl" xlink:title="label: CommonStockMember to us-gaap_CommonStockMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesIssued" xlink:label="CommonStockSharesIssued" xlink:title="CommonStockSharesIssued" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesIssued_lbl" xml:lang="en-US" id="us-gaap_CommonStockSharesIssued_lbl">Common stock, shares issued (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesIssued" xlink:to="us-gaap_CommonStockSharesIssued_lbl" xlink:title="label: CommonStockSharesIssued to us-gaap_CommonStockSharesIssued_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesIssued_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesIssued_lbl1">Common Stock, Shares, Issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesIssued" xlink:to="us-gaap_CommonStockSharesIssued_lbl1" xlink:title="label: CommonStockSharesIssued to us-gaap_CommonStockSharesIssued_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare" xlink:label="CommonStockParOrStatedValuePerShare" xlink:title="CommonStockParOrStatedValuePerShare" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockParOrStatedValuePerShare_lbl" xml:lang="en-US" id="us-gaap_CommonStockParOrStatedValuePerShare_lbl">Common stock, par value (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockParOrStatedValuePerShare" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare_lbl" xlink:title="label: CommonStockParOrStatedValuePerShare to us-gaap_CommonStockParOrStatedValuePerShare_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockParOrStatedValuePerShare_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockParOrStatedValuePerShare_lbl1" xml:lang="en-US" id="us-gaap_CommonStockParOrStatedValuePerShare_lbl1">Common Stock, Par or Stated Value Per Share</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockParOrStatedValuePerShare" xlink:to="us-gaap_CommonStockParOrStatedValuePerShare_lbl1" xlink:title="label: CommonStockParOrStatedValuePerShare to us-gaap_CommonStockParOrStatedValuePerShare_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockValue" xlink:label="CommonStockValue" xlink:title="CommonStockValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockValue_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CommonStockValue_lbl" xml:lang="en-US" id="us-gaap_CommonStockValue_lbl">Common stock, $0.001 par value; 300,000,000 shares authorized, 141,753,122 and 141,210,015 shares issued and outstanding at March 31, 2022 (unaudited) and December 31, 2021, respectively</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockValue" xlink:to="us-gaap_CommonStockValue_lbl" xlink:title="label: CommonStockValue to us-gaap_CommonStockValue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockValue_lbl1" xml:lang="en-US" id="us-gaap_CommonStockValue_lbl1">Common Stock, Value, Issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockValue" xlink:to="us-gaap_CommonStockValue_lbl1" xlink:title="label: CommonStockValue to us-gaap_CommonStockValue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesAuthorized" xlink:label="CommonStockSharesAuthorized" xlink:title="CommonStockSharesAuthorized" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesAuthorized_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesAuthorized_lbl" xml:lang="en-US" id="us-gaap_CommonStockSharesAuthorized_lbl">Common stock, shares authorized (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesAuthorized" xlink:to="us-gaap_CommonStockSharesAuthorized_lbl" xlink:title="label: CommonStockSharesAuthorized to us-gaap_CommonStockSharesAuthorized_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesAuthorized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesAuthorized_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesAuthorized_lbl1">Common Stock, Shares Authorized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesAuthorized" xlink:to="us-gaap_CommonStockSharesAuthorized_lbl1" xlink:title="label: CommonStockSharesAuthorized to us-gaap_CommonStockSharesAuthorized_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesOutstanding" xlink:label="CommonStockSharesOutstanding" xlink:title="CommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesOutstanding_lbl" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding_lbl">Common stock, shares outstanding (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesOutstanding" xlink:to="us-gaap_CommonStockSharesOutstanding_lbl" xlink:title="label: CommonStockSharesOutstanding to us-gaap_CommonStockSharesOutstanding_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesOutstanding_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding_lbl1">Common Stock, Shares, Outstanding</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesOutstanding" xlink:to="us-gaap_CommonStockSharesOutstanding_lbl1" xlink:title="label: CommonStockSharesOutstanding to us-gaap_CommonStockSharesOutstanding_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="ComprehensiveIncomeNetOfTax" xlink:title="ComprehensiveIncomeNetOfTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_ComprehensiveIncomeNetOfTax_lbl" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTax_lbl">Comprehensive loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_ComprehensiveIncomeNetOfTax_lbl" xlink:title="label: ComprehensiveIncomeNetOfTax to us-gaap_ComprehensiveIncomeNetOfTax_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ComprehensiveIncomeNetOfTax_lbl1" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTax_lbl1">Comprehensive Income (Loss), Net of Tax, Attributable to Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_ComprehensiveIncomeNetOfTax_lbl1" xlink:title="label: ComprehensiveIncomeNetOfTax to us-gaap_ComprehensiveIncomeNetOfTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskTypeDomain_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskTypeDomain_lbl">Concentration Risk Type [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskTypeDomain" xlink:to="us-gaap_ConcentrationRiskTypeDomain_lbl" xlink:title="label: ConcentrationRiskTypeDomain to us-gaap_ConcentrationRiskTypeDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskPercentage1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskPercentage1_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskPercentage1_lbl">Concentration percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskPercentage1" xlink:to="us-gaap_ConcentrationRiskPercentage1_lbl" xlink:title="label: ConcentrationRiskPercentage1 to us-gaap_ConcentrationRiskPercentage1_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskBenchmarkDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskBenchmarkDomain_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskBenchmarkDomain_lbl">Concentration Risk Benchmark [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskBenchmarkDomain" xlink:to="us-gaap_ConcentrationRiskBenchmarkDomain_lbl" xlink:title="label: ConcentrationRiskBenchmarkDomain to us-gaap_ConcentrationRiskBenchmarkDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskByTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskByTypeAxis_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskByTypeAxis_lbl">Concentration Risk Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskByTypeAxis" xlink:to="us-gaap_ConcentrationRiskByTypeAxis_lbl" xlink:title="label: ConcentrationRiskByTypeAxis to us-gaap_ConcentrationRiskByTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl">Concentration Risk Benchmark [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskByBenchmarkAxis" xlink:to="us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" xlink:title="label: ConcentrationRiskByBenchmarkAxis to us-gaap_ConcentrationRiskByBenchmarkAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConsolidationPolicyTextBlock" xlink:label="ConsolidationPolicyTextBlock" xlink:title="ConsolidationPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConsolidationPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConsolidationPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_ConsolidationPolicyTextBlock_lbl">Consolidation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationPolicyTextBlock" xlink:to="us-gaap_ConsolidationPolicyTextBlock_lbl" xlink:title="label: ConsolidationPolicyTextBlock to us-gaap_ConsolidationPolicyTextBlock_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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 Debt, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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 Senior Notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock_lbl" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock_lbl1">Convertible Debt [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl">Expenses:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl1">Costs and Expenses [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl">Less than 12 months of temporary impairment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl1">Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, Less than 12 Months</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl">More than 12 months of temporary impairment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl1">Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, 12 Months or Longer</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl">Number of investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl1">Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, Less than 12 Months, Number of Positions</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:label="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:title="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl">Total temporary impairment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleUnrealizedLossPosition to us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl1">Debt Securities, Available-for-sale, Unrealized Loss Position</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleUnrealizedLossPosition to us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTotalLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl">Total temporary impairment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss to us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl1">Debt Securities, Available-for-sale, Unrealized Loss Position, Accumulated Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss to us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl">Less than 12 months of temporary impairment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1">Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, Less than 12 Months, Accumulated Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl">More than 12 months of temporary impairment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1">Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, 12 Months or Longer, Accumulated Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss to us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtPolicyTextBlock" xlink:label="DebtPolicyTextBlock" xlink:title="DebtPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_DebtPolicyTextBlock_lbl">Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtPolicyTextBlock" xlink:to="us-gaap_DebtPolicyTextBlock_lbl" xlink:title="label: DebtPolicyTextBlock to us-gaap_DebtPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DebtPolicyTextBlock_lbl1">Debt, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtPolicyTextBlock" xlink:to="us-gaap_DebtPolicyTextBlock_lbl1" xlink:title="label: DebtPolicyTextBlock to us-gaap_DebtPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesMember_lbl">Available-for-sale Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesMember" xlink:to="us-gaap_DebtSecuritiesMember_lbl" xlink:title="label: DebtSecuritiesMember to us-gaap_DebtSecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesMember_lbl1">Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesMember" xlink:to="us-gaap_DebtSecuritiesMember_lbl1" xlink:title="label: DebtSecuritiesMember to us-gaap_DebtSecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredFinanceCostsNet" xlink:to="us-gaap_DeferredFinanceCostsNet_lbl" xlink:title="label: DeferredFinanceCostsNet to us-gaap_DeferredFinanceCostsNet_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredFinanceCostsNet" xlink:to="us-gaap_DeferredFinanceCostsNet_lbl1" xlink:title="label: DeferredFinanceCostsNet to us-gaap_DeferredFinanceCostsNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Depreciation" xlink:label="Depreciation" xlink:title="Depreciation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Depreciation_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_Depreciation_lbl" xml:lang="en-US" id="us-gaap_Depreciation_lbl">Depreciation</link:label>
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Depreciation" xlink:to="us-gaap_Depreciation_lbl1" xlink:title="label: Depreciation to us-gaap_Depreciation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativesPolicyTextBlock" xlink:label="DerivativesPolicyTextBlock" xlink:title="DerivativesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DerivativesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DerivativesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_DerivativesPolicyTextBlock_lbl">Call Spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DerivativesPolicyTextBlock" xlink:to="us-gaap_DerivativesPolicyTextBlock_lbl" xlink:title="label: DerivativesPolicyTextBlock to us-gaap_DerivativesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DerivativesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DerivativesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DerivativesPolicyTextBlock_lbl1">Derivatives, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DerivativesPolicyTextBlock" xlink:to="us-gaap_DerivativesPolicyTextBlock_lbl1" xlink:title="label: DerivativesPolicyTextBlock to us-gaap_DerivativesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerSharePolicyTextBlock" xlink:label="EarningsPerSharePolicyTextBlock" xlink:title="EarningsPerSharePolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerSharePolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EarningsPerSharePolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_EarningsPerSharePolicyTextBlock_lbl">Basic and Diluted Net Loss per Share</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EarningsPerSharePolicyTextBlock" xlink:to="us-gaap_EarningsPerSharePolicyTextBlock_lbl" xlink:title="label: EarningsPerSharePolicyTextBlock to us-gaap_EarningsPerSharePolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerSharePolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerSharePolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_EarningsPerSharePolicyTextBlock_lbl1">Earnings Per Share, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EarningsPerSharePolicyTextBlock" xlink:to="us-gaap_EarningsPerSharePolicyTextBlock_lbl1" xlink:title="label: EarningsPerSharePolicyTextBlock to us-gaap_EarningsPerSharePolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasic" xlink:label="EarningsPerShareBasic" xlink:title="EarningsPerShareBasic" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareBasic_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerShareBasic_lbl" xml:lang="en-US" id="us-gaap_EarningsPerShareBasic_lbl">Basic net loss 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="EarningsPerShareBasic" xlink:to="us-gaap_EarningsPerShareBasic_lbl" xlink:title="label: EarningsPerShareBasic to us-gaap_EarningsPerShareBasic_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasicAbstract" xlink:label="EarningsPerShareBasicAbstract" xlink:title="EarningsPerShareBasicAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareBasicAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerShareBasicAbstract_lbl" xml:lang="en-US" id="us-gaap_EarningsPerShareBasicAbstract_lbl">Basic Net Loss per Share [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EarningsPerShareBasicAbstract" xlink:to="us-gaap_EarningsPerShareBasicAbstract_lbl" xlink:title="label: EarningsPerShareBasicAbstract to us-gaap_EarningsPerShareBasicAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareDiluted" xlink:label="EarningsPerShareDiluted" xlink:title="EarningsPerShareDiluted" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareDiluted_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerShareDiluted_lbl" xml:lang="en-US" id="us-gaap_EarningsPerShareDiluted_lbl">Diluted net loss 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="EarningsPerShareDiluted" xlink:to="us-gaap_EarningsPerShareDiluted_lbl" xlink:title="label: EarningsPerShareDiluted to us-gaap_EarningsPerShareDiluted_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasicLineItems" xlink:label="EarningsPerShareBasicLineItems" xlink:title="EarningsPerShareBasicLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareBasicLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerShareBasicLineItems_lbl" xml:lang="en-US" id="us-gaap_EarningsPerShareBasicLineItems_lbl">Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EarningsPerShareBasicLineItems" xlink:to="us-gaap_EarningsPerShareBasicLineItems_lbl" xlink:title="label: EarningsPerShareBasicLineItems to us-gaap_EarningsPerShareBasicLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents" xlink:label="EffectOfExchangeRateOnCashAndCashEquivalents" xlink:title="EffectOfExchangeRateOnCashAndCashEquivalents" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl" xml:lang="en-US" id="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl">Effects of exchange rates on cash</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectOfExchangeRateOnCashAndCashEquivalents" xlink:to="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl" xlink:title="label: EffectOfExchangeRateOnCashAndCashEquivalents to us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl1" xml:lang="en-US" id="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl1">Effect of Exchange Rate on Cash and Cash Equivalents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectOfExchangeRateOnCashAndCashEquivalents" xlink:to="us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl1" xlink:title="label: EffectOfExchangeRateOnCashAndCashEquivalents to us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockMember" xlink:label="EmployeeStockMember" xlink:title="EmployeeStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeStockMember_lbl" xml:lang="en-US" id="us-gaap_EmployeeStockMember_lbl">ESPP [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockMember" xlink:to="us-gaap_EmployeeStockMember_lbl" xlink:title="label: EmployeeStockMember to us-gaap_EmployeeStockMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeStockMember_lbl1" xml:lang="en-US" id="us-gaap_EmployeeStockMember_lbl1">Employee Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockMember" xlink:to="us-gaap_EmployeeStockMember_lbl1" xlink:title="label: EmployeeStockMember to us-gaap_EmployeeStockMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl">Weighted average period for recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1">Share-based Payment Arrangement, Nonvested Award, Cost Not yet Recognized, Period for Recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="EmployeeStockOptionMember" xlink:title="EmployeeStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeStockOptionMember_lbl" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl">Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeStockOptionMember_lbl1" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl1">Share-based Payment Arrangement, Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl1" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl">Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl">Unrecognized compensation cost related to non-vested units</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl1" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl1">Share-based Payment Arrangement, Nonvested Award, Excluding Option, Cost Not yet Recognized, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="EmployeeRelatedLiabilitiesCurrent" xlink:title="EmployeeRelatedLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl" xml:lang="en-US" id="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl">Accrued compensation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeRelatedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl" xlink:title="label: EmployeeRelatedLiabilitiesCurrent to us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1">Employee-related Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeRelatedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xlink:title="label: EmployeeRelatedLiabilitiesCurrent to us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract_lbl" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract_lbl">Unrecognized Compensation Expense [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl">Unrecognized compensation expense related to non-vested stock options</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl1" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl1">Share-based Payment Arrangement, Nonvested Award, Option, Cost Not yet Recognized, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EntityWideRevenueMajorCustomerLineItems" xlink:label="EntityWideRevenueMajorCustomerLineItems" xlink:title="EntityWideRevenueMajorCustomerLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl" xml:lang="en-US" id="us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl">Revenue, Major Customer [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityWideRevenueMajorCustomerLineItems" xlink:to="us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl" xlink:title="label: EntityWideRevenueMajorCustomerLineItems to us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="EquityComponentDomain" xlink:title="EquityComponentDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquityComponentDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquityComponentDomain_lbl" xml:lang="en-US" id="us-gaap_EquityComponentDomain_lbl">Equity Component [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityComponentDomain" xlink:to="us-gaap_EquityComponentDomain_lbl" xlink:title="label: EquityComponentDomain to us-gaap_EquityComponentDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiUnrealizedGain" xlink:label="EquitySecuritiesFvNiUnrealizedGain" xlink:title="EquitySecuritiesFvNiUnrealizedGain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl">Gross unrealized gains</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiUnrealizedGain" xlink:to="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl" xlink:title="label: EquitySecuritiesFvNiUnrealizedGain to us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl1">Equity Securities, FV-NI, Unrealized Gain</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiUnrealizedGain" xlink:to="us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl1" xlink:title="label: EquitySecuritiesFvNiUnrealizedGain to us-gaap_EquitySecuritiesFvNiUnrealizedGain_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiUnrealizedLoss" xlink:label="EquitySecuritiesFvNiUnrealizedLoss" xlink:title="EquitySecuritiesFvNiUnrealizedLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl">Gross unrealized losses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiUnrealizedLoss" xlink:to="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl" xlink:title="label: EquitySecuritiesFvNiUnrealizedLoss to us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1">Equity Securities, FV-NI, Unrealized Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiUnrealizedLoss" xlink:to="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xlink:title="label: EquitySecuritiesFvNiUnrealizedLoss to us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNi" xlink:label="EquitySecuritiesFvNi" xlink:title="EquitySecuritiesFvNi" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNi_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesFvNi_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNi_lbl">Investment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNi" xlink:to="us-gaap_EquitySecuritiesFvNi_lbl" xlink:title="label: EquitySecuritiesFvNi to us-gaap_EquitySecuritiesFvNi_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNi_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_EquitySecuritiesFvNi_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNi_lbl1">Estimated fair value</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNi" xlink:to="us-gaap_EquitySecuritiesFvNi_lbl1" xlink:title="label: EquitySecuritiesFvNi to us-gaap_EquitySecuritiesFvNi_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNi_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNi_lbl2" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNi_lbl2">Equity Securities, FV-NI, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNi" xlink:to="us-gaap_EquitySecuritiesFvNi_lbl2" xlink:title="label: EquitySecuritiesFvNi to us-gaap_EquitySecuritiesFvNi_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiCost" xlink:label="EquitySecuritiesFvNiCost" xlink:title="EquitySecuritiesFvNiCost" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiCost_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesFvNiCost_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiCost_lbl">Amortized cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiCost" xlink:to="us-gaap_EquitySecuritiesFvNiCost_lbl" xlink:title="label: EquitySecuritiesFvNiCost to us-gaap_EquitySecuritiesFvNiCost_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiCost_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNiCost_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiCost_lbl1">Equity Securities, FV-NI, Cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiCost" xlink:to="us-gaap_EquitySecuritiesFvNiCost_lbl1" xlink:title="label: EquitySecuritiesFvNiCost to us-gaap_EquitySecuritiesFvNiCost_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesMember" xlink:label="EquitySecuritiesMember" xlink:title="EquitySecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesMember_lbl">Equity Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesMember" xlink:to="us-gaap_EquitySecuritiesMember_lbl" xlink:title="label: EquitySecuritiesMember to us-gaap_EquitySecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesMember_lbl1">Equity Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesMember" xlink:to="us-gaap_EquitySecuritiesMember_lbl1" xlink:title="label: EquitySecuritiesMember to us-gaap_EquitySecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="FairValueNetAssetLiabilityAbstract" xlink:title="FairValueNetAssetLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract_lbl">Fair Value Measurements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract_lbl" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1">Fair Value, Net Asset (Liability) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" xlink:title="label: FairValueNetAssetLiabilityAbstract to us-gaap_FairValueNetAssetLiabilityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" xml:lang="en-US" id="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl">Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" xlink:title="label: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl1" xml:lang="en-US" id="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl1">Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl1" xlink:title="label: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="FairValueByFairValueHierarchyLevelAxis" xlink:title="FairValueByFairValueHierarchyLevelAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueByFairValueHierarchyLevelAxis_lbl" xml:lang="en-US" id="us-gaap_FairValueByFairValueHierarchyLevelAxis_lbl">Fair Value, Hierarchy [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis_lbl" xlink:title="label: FairValueByFairValueHierarchyLevelAxis to us-gaap_FairValueByFairValueHierarchyLevelAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueDisclosuresAbstract" xlink:label="FairValueDisclosuresAbstract" xlink:title="FairValueDisclosuresAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueDisclosuresAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueDisclosuresAbstract_lbl" xml:lang="en-US" id="us-gaap_FairValueDisclosuresAbstract_lbl">Fair Value Measurements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueDisclosuresAbstract" xlink:to="us-gaap_FairValueDisclosuresAbstract_lbl" xlink:title="label: FairValueDisclosuresAbstract to us-gaap_FairValueDisclosuresAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="FairValueByMeasurementFrequencyAxis" xlink:title="FairValueByMeasurementFrequencyAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueByMeasurementFrequencyAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueByMeasurementFrequencyAxis_lbl" xml:lang="en-US" id="us-gaap_FairValueByMeasurementFrequencyAxis_lbl">Measurement Frequency [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueByMeasurementFrequencyAxis" xlink:to="us-gaap_FairValueByMeasurementFrequencyAxis_lbl" xlink:title="label: FairValueByMeasurementFrequencyAxis to us-gaap_FairValueByMeasurementFrequencyAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_lbl" xml:lang="en-US" id="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_lbl">Fair Value Measurements, Recurring and Nonrecurring [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_lbl" xlink:title="label: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="FairValueMeasurementsFairValueHierarchyDomain" xlink:title="FairValueMeasurementsFairValueHierarchyDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_lbl" xml:lang="en-US" id="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_lbl">Fair Value Hierarchy [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_lbl" xlink:title="label: FairValueMeasurementsFairValueHierarchyDomain to us-gaap_FairValueMeasurementsFairValueHierarchyDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsRecurringMember" xlink:label="FairValueMeasurementsRecurringMember" xlink:title="FairValueMeasurementsRecurringMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueMeasurementsRecurringMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueMeasurementsRecurringMember_lbl" xml:lang="en-US" id="us-gaap_FairValueMeasurementsRecurringMember_lbl">Recurring Basis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueMeasurementsRecurringMember" xlink:to="us-gaap_FairValueMeasurementsRecurringMember_lbl" xlink:title="label: FairValueMeasurementsRecurringMember to us-gaap_FairValueMeasurementsRecurringMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueMeasurementsRecurringMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueMeasurementsRecurringMember_lbl1" xml:lang="en-US" id="us-gaap_FairValueMeasurementsRecurringMember_lbl1">Fair Value, Recurring [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueMeasurementsRecurringMember" xlink:to="us-gaap_FairValueMeasurementsRecurringMember_lbl1" xlink:title="label: FairValueMeasurementsRecurringMember to us-gaap_FairValueMeasurementsRecurringMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="FairValueMeasurementFrequencyDomain" xlink:title="FairValueMeasurementFrequencyDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueMeasurementFrequencyDomain_lbl" xml:lang="en-US" id="us-gaap_FairValueMeasurementFrequencyDomain_lbl">Fair Value, Measurement Frequency [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueMeasurementFrequencyDomain" xlink:to="us-gaap_FairValueMeasurementFrequencyDomain_lbl" xlink:title="label: FairValueMeasurementFrequencyDomain to us-gaap_FairValueMeasurementFrequencyDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueDisclosuresTextBlock" xlink:label="FairValueDisclosuresTextBlock" xlink:title="FairValueDisclosuresTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueDisclosuresTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueDisclosuresTextBlock_lbl" xml:lang="en-US" id="us-gaap_FairValueDisclosuresTextBlock_lbl">Fair Value Measurements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueDisclosuresTextBlock" xlink:to="us-gaap_FairValueDisclosuresTextBlock_lbl" xlink:title="label: FairValueDisclosuresTextBlock to us-gaap_FairValueDisclosuresTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueDisclosuresTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueDisclosuresTextBlock_lbl1" xml:lang="en-US" id="us-gaap_FairValueDisclosuresTextBlock_lbl1">Fair Value Disclosures [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueDisclosuresTextBlock" xlink:to="us-gaap_FairValueDisclosuresTextBlock_lbl1" xlink:title="label: FairValueDisclosuresTextBlock to us-gaap_FairValueDisclosuresTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock" xlink:label="FairValueAssetsMeasuredOnRecurringBasisTextBlock" xlink:title="FairValueAssetsMeasuredOnRecurringBasisTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl" xml:lang="en-US" id="us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl">Assets Measured at Fair Value on a Recurring Basis</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueAssetsMeasuredOnRecurringBasisTextBlock" xlink:to="us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl" xlink:title="label: FairValueAssetsMeasuredOnRecurringBasisTextBlock to us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl1" xml:lang="en-US" id="us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl1">Fair Value, Assets Measured on Recurring Basis [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueAssetsMeasuredOnRecurringBasisTextBlock" xlink:to="us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl1" xlink:title="label: FairValueAssetsMeasuredOnRecurringBasisTextBlock to us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel1Member" xlink:label="FairValueInputsLevel1Member" xlink:title="FairValueInputsLevel1Member" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel1Member_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueInputsLevel1Member_lbl" xml:lang="en-US" id="us-gaap_FairValueInputsLevel1Member_lbl">Quoted Prices in Active Markets (Level 1) [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueInputsLevel1Member" xlink:to="us-gaap_FairValueInputsLevel1Member_lbl" xlink:title="label: FairValueInputsLevel1Member to us-gaap_FairValueInputsLevel1Member_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueInputsLevel1Member" xlink:to="us-gaap_FairValueInputsLevel1Member_lbl1" xlink:title="label: FairValueInputsLevel1Member to us-gaap_FairValueInputsLevel1Member_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel2Member" xlink:label="FairValueInputsLevel2Member" xlink:title="FairValueInputsLevel2Member" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel2Member_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueInputsLevel2Member_lbl" xml:lang="en-US" id="us-gaap_FairValueInputsLevel2Member_lbl">Significant Other Observable Inputs (Level 2) [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueInputsLevel2Member" xlink:to="us-gaap_FairValueInputsLevel2Member_lbl" xlink:title="label: FairValueInputsLevel2Member to us-gaap_FairValueInputsLevel2Member_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel2Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueInputsLevel2Member_lbl1" xml:lang="en-US" id="us-gaap_FairValueInputsLevel2Member_lbl1">Fair Value, Inputs, Level 2 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueInputsLevel2Member" xlink:to="us-gaap_FairValueInputsLevel2Member_lbl1" xlink:title="label: FairValueInputsLevel2Member to us-gaap_FairValueInputsLevel2Member_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="FairValueInputsLevel3Member" xlink:title="FairValueInputsLevel3Member" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel3Member_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueInputsLevel3Member_lbl" xml:lang="en-US" id="us-gaap_FairValueInputsLevel3Member_lbl">Significant Unobservable Inputs (Level 3) [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueInputsLevel3Member" xlink:to="us-gaap_FairValueInputsLevel3Member_lbl" xlink:title="label: FairValueInputsLevel3Member to us-gaap_FairValueInputsLevel3Member_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel3Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueInputsLevel3Member_lbl1" xml:lang="en-US" id="us-gaap_FairValueInputsLevel3Member_lbl1">Fair Value, Inputs, Level 3 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueInputsLevel3Member" xlink:to="us-gaap_FairValueInputsLevel3Member_lbl1" xlink:title="label: FairValueInputsLevel3Member to us-gaap_FairValueInputsLevel3Member_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FinancialInstrumentAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FinancialInstrumentAxis_lbl" xml:lang="en-US" id="us-gaap_FinancialInstrumentAxis_lbl">Financial Instrument [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FinancialInstrumentAxis" xlink:to="us-gaap_FinancialInstrumentAxis_lbl" xlink:title="label: FinancialInstrumentAxis to us-gaap_FinancialInstrumentAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="FiniteLivedIntangibleAssetsNet" xlink:title="FiniteLivedIntangibleAssetsNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FiniteLivedIntangibleAssetsNet_lbl" xml:lang="en-US" id="us-gaap_FiniteLivedIntangibleAssetsNet_lbl">Patents, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet_lbl" xlink:title="label: FiniteLivedIntangibleAssetsNet to us-gaap_FiniteLivedIntangibleAssetsNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FiniteLivedIntangibleAssetsNet_lbl1" xml:lang="en-US" id="us-gaap_FiniteLivedIntangibleAssetsNet_lbl1">Finite-Lived Intangible Assets, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet_lbl1" xlink:title="label: FiniteLivedIntangibleAssetsNet to us-gaap_FiniteLivedIntangibleAssetsNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GranteeStatusDomain" xlink:label="GranteeStatusDomain" xlink:title="GranteeStatusDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GranteeStatusDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GranteeStatusDomain_lbl" xml:lang="en-US" id="us-gaap_GranteeStatusDomain_lbl">Grantee Status [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GranteeStatusDomain" xlink:to="us-gaap_GranteeStatusDomain_lbl" xlink:title="label: GranteeStatusDomain to us-gaap_GranteeStatusDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GranteeStatusAxis" xlink:label="GranteeStatusAxis" xlink:title="GranteeStatusAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GranteeStatusAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GranteeStatusAxis_lbl" xml:lang="en-US" id="us-gaap_GranteeStatusAxis_lbl">Grantee Status [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GranteeStatusAxis" xlink:to="us-gaap_GranteeStatusAxis_lbl" xlink:title="label: GranteeStatusAxis to us-gaap_GranteeStatusAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnDispositionOfAssets" xlink:label="GainLossOnDispositionOfAssets" xlink:title="GainLossOnDispositionOfAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnDispositionOfAssets_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_GainLossOnDispositionOfAssets_lbl" xml:lang="en-US" id="us-gaap_GainLossOnDispositionOfAssets_lbl">Non-cash losses related to disposal of property, plant and equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnDispositionOfAssets" xlink:to="us-gaap_GainLossOnDispositionOfAssets_lbl" xlink:title="label: GainLossOnDispositionOfAssets to us-gaap_GainLossOnDispositionOfAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnDispositionOfAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GainLossOnDispositionOfAssets_lbl1" xml:lang="en-US" id="us-gaap_GainLossOnDispositionOfAssets_lbl1">Gain (Loss) on Disposition of Property Plant Equipment, Excluding Oil and Gas Property and Timber Property</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnDispositionOfAssets" xlink:to="us-gaap_GainLossOnDispositionOfAssets_lbl1" xlink:title="label: GainLossOnDispositionOfAssets to us-gaap_GainLossOnDispositionOfAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnInvestments" xlink:label="GainLossOnInvestments" xlink:title="GainLossOnInvestments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnInvestments_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_GainLossOnInvestments_lbl" xml:lang="en-US" id="us-gaap_GainLossOnInvestments_lbl">Loss on investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnInvestments" xlink:to="us-gaap_GainLossOnInvestments_lbl" xlink:title="label: GainLossOnInvestments to us-gaap_GainLossOnInvestments_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnInvestments_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_GainLossOnInvestments_lbl1" xml:lang="en-US" id="us-gaap_GainLossOnInvestments_lbl1">Gain on investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnInvestments" xlink:to="us-gaap_GainLossOnInvestments_lbl1" xlink:title="label: GainLossOnInvestments to us-gaap_GainLossOnInvestments_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnInvestments_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GainLossOnInvestments_lbl2" xml:lang="en-US" id="us-gaap_GainLossOnInvestments_lbl2">Gain (Loss) on Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnInvestments" xlink:to="us-gaap_GainLossOnInvestments_lbl2" xlink:title="label: GainLossOnInvestments to us-gaap_GainLossOnInvestments_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt" xlink:label="GainsLossesOnExtinguishmentOfDebt" xlink:title="GainsLossesOnExtinguishmentOfDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl" xml:lang="en-US" id="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl">Loss on early retirement of debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainsLossesOnExtinguishmentOfDebt" xlink:to="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl" xlink:title="label: GainsLossesOnExtinguishmentOfDebt to us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1" xml:lang="en-US" id="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1">Gain (Loss) on Extinguishment of Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainsLossesOnExtinguishmentOfDebt" xlink:to="us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1" xlink:title="label: GainsLossesOnExtinguishmentOfDebt to us-gaap_GainsLossesOnExtinguishmentOfDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" xlink:label="ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" xlink:title="ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl">Long-Lived Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" xlink:to="us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl" xlink:title="label: ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock to us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl1">Impairment or Disposal of Long-Lived Assets, Including Intangible Assets, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" xlink:to="us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl1" xlink:title="label: ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock to us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ImpairmentOfIntangibleAssetsFinitelived" xlink:label="ImpairmentOfIntangibleAssetsFinitelived" xlink:title="ImpairmentOfIntangibleAssetsFinitelived" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl" xml:lang="en-US" id="us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl">Non-cash losses related to patents</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImpairmentOfIntangibleAssetsFinitelived" xlink:to="us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl" xlink:title="label: ImpairmentOfIntangibleAssetsFinitelived to us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl1" xml:lang="en-US" id="us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl1">Impairment of Intangible Assets, Finite-lived</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImpairmentOfIntangibleAssetsFinitelived" xlink:to="us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl1" xlink:title="label: ImpairmentOfIntangibleAssetsFinitelived to us-gaap_ImpairmentOfIntangibleAssetsFinitelived_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:title="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl" xml:lang="en-US" id="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl">Loss before income tax expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl" xlink:title="label: IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest to us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl1" xml:lang="en-US" id="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl1">Income (Loss) from Continuing Operations before Income Taxes, Noncontrolling Interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl1" xlink:title="label: IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest to us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="IncomeStatementLocationDomain" xlink:title="IncomeStatementLocationDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeStatementLocationDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeStatementLocationDomain_lbl" xml:lang="en-US" id="us-gaap_IncomeStatementLocationDomain_lbl">Income Statement Location [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeStatementLocationDomain" xlink:to="us-gaap_IncomeStatementLocationDomain_lbl" xlink:title="label: IncomeStatementLocationDomain to us-gaap_IncomeStatementLocationDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxDisclosureAbstract" xlink:label="IncomeTaxDisclosureAbstract" xlink:title="IncomeTaxDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_IncomeTaxDisclosureAbstract_lbl">Income Taxes [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxDisclosureAbstract" xlink:to="us-gaap_IncomeTaxDisclosureAbstract_lbl" xlink:title="label: IncomeTaxDisclosureAbstract to us-gaap_IncomeTaxDisclosureAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="IncomeStatementLocationAxis" xlink:title="IncomeStatementLocationAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeStatementLocationAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeStatementLocationAxis_lbl" xml:lang="en-US" id="us-gaap_IncomeStatementLocationAxis_lbl">Income Statement Location [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationAxis_lbl" xlink:title="label: IncomeStatementLocationAxis to us-gaap_IncomeStatementLocationAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementAbstract" xlink:label="IncomeStatementAbstract" xlink:title="IncomeStatementAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeStatementAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeStatementAbstract_lbl" xml:lang="en-US" id="us-gaap_IncomeStatementAbstract_lbl">CONSOLIDATED STATEMENTS OF OPERATIONS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeStatementAbstract" xlink:to="us-gaap_IncomeStatementAbstract_lbl" xlink:title="label: IncomeStatementAbstract to us-gaap_IncomeStatementAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxDisclosureTextBlock" xlink:label="IncomeTaxDisclosureTextBlock" xlink:title="IncomeTaxDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_IncomeTaxDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_IncomeTaxDisclosureTextBlock_lbl">Income Taxes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxDisclosureTextBlock" xlink:to="us-gaap_IncomeTaxDisclosureTextBlock_lbl" xlink:title="label: IncomeTaxDisclosureTextBlock to us-gaap_IncomeTaxDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_IncomeTaxDisclosureTextBlock_lbl1">Income Tax Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxDisclosureTextBlock" xlink:to="us-gaap_IncomeTaxDisclosureTextBlock_lbl1" xlink:title="label: IncomeTaxDisclosureTextBlock to us-gaap_IncomeTaxDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="IncomeTaxExpenseBenefit" xlink:title="IncomeTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxExpenseBenefit_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_IncomeTaxExpenseBenefit_lbl" xml:lang="en-US" id="us-gaap_IncomeTaxExpenseBenefit_lbl">Income tax expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxExpenseBenefit" xlink:to="us-gaap_IncomeTaxExpenseBenefit_lbl" xlink:title="label: IncomeTaxExpenseBenefit to us-gaap_IncomeTaxExpenseBenefit_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxExpenseBenefit_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncomeTaxExpenseBenefit_lbl1" xml:lang="en-US" id="us-gaap_IncomeTaxExpenseBenefit_lbl1">Income tax expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxExpenseBenefit" xlink:to="us-gaap_IncomeTaxExpenseBenefit_lbl1" xlink:title="label: IncomeTaxExpenseBenefit to us-gaap_IncomeTaxExpenseBenefit_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxExpenseBenefit_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxExpenseBenefit_lbl2" xml:lang="en-US" id="us-gaap_IncomeTaxExpenseBenefit_lbl2">Income Tax Expense (Benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxExpenseBenefit" xlink:to="us-gaap_IncomeTaxExpenseBenefit_lbl2" xlink:title="label: IncomeTaxExpenseBenefit to us-gaap_IncomeTaxExpenseBenefit_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxPolicyTextBlock" xlink:label="IncomeTaxPolicyTextBlock" xlink:title="IncomeTaxPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncomeTaxPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_IncomeTaxPolicyTextBlock_lbl">Income Taxes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxPolicyTextBlock" xlink:to="us-gaap_IncomeTaxPolicyTextBlock_lbl" xlink:title="label: IncomeTaxPolicyTextBlock to us-gaap_IncomeTaxPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_IncomeTaxPolicyTextBlock_lbl1">Income Tax, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxPolicyTextBlock" xlink:to="us-gaap_IncomeTaxPolicyTextBlock_lbl1" xlink:title="label: IncomeTaxPolicyTextBlock to us-gaap_IncomeTaxPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxesPaid" xlink:label="IncomeTaxesPaid" xlink:title="IncomeTaxesPaid" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxesPaid_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncomeTaxesPaid_lbl" xml:lang="en-US" id="us-gaap_IncomeTaxesPaid_lbl">Income taxes paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxesPaid" xlink:to="us-gaap_IncomeTaxesPaid_lbl" xlink:title="label: IncomeTaxesPaid to us-gaap_IncomeTaxesPaid_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxesPaid_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxesPaid_lbl1" xml:lang="en-US" id="us-gaap_IncomeTaxesPaid_lbl1">Income Taxes Paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxesPaid" xlink:to="us-gaap_IncomeTaxesPaid_lbl1" xlink:title="label: IncomeTaxesPaid to us-gaap_IncomeTaxesPaid_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerAsset" xlink:label="IncreaseDecreaseInContractWithCustomerAsset" xlink:title="IncreaseDecreaseInContractWithCustomerAsset" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl">Contracts receivable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInContractWithCustomerAsset" xlink:to="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl" xlink:title="label: IncreaseDecreaseInContractWithCustomerAsset to us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl1">Increase (Decrease) in Contract with Customer, Asset</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInContractWithCustomerAsset" xlink:to="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl1" xlink:title="label: IncreaseDecreaseInContractWithCustomerAsset to us-gaap_IncreaseDecreaseInContractWithCustomerAsset_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherCurrentLiabilities" xlink:label="IncreaseDecreaseInOtherCurrentLiabilities" xlink:title="IncreaseDecreaseInOtherCurrentLiabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl">Accrued liabilities and other current liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherCurrentLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl" xlink:title="label: IncreaseDecreaseInOtherCurrentLiabilities to us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl1">Increase (Decrease) in Other Current Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherCurrentLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl1" xlink:title="label: IncreaseDecreaseInOtherCurrentLiabilities to us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability" xlink:label="IncreaseDecreaseInContractWithCustomerLiability" xlink:title="IncreaseDecreaseInContractWithCustomerLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl">Deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInContractWithCustomerLiability" xlink:to="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl" xlink:title="label: IncreaseDecreaseInContractWithCustomerLiability to us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl1">Increase (Decrease) in Contract with Customer, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInContractWithCustomerLiability" xlink:to="us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl1" xlink:title="label: IncreaseDecreaseInContractWithCustomerLiability to us-gaap_IncreaseDecreaseInContractWithCustomerLiability_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:label="IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:title="IncreaseDecreaseInAccruedIncomeTaxesPayable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl">Income taxes receivable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:to="us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl" xlink:title="label: IncreaseDecreaseInAccruedIncomeTaxesPayable to us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl1">Increase (Decrease) in Income Taxes Payable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:to="us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl1" xlink:title="label: IncreaseDecreaseInAccruedIncomeTaxesPayable to us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="IncreaseDecreaseInAccountsPayable" xlink:title="IncreaseDecreaseInAccountsPayable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInAccountsPayable_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInAccountsPayable_lbl">Accounts payable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccountsPayable" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayable_lbl" xlink:title="label: IncreaseDecreaseInAccountsPayable to us-gaap_IncreaseDecreaseInAccountsPayable_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInAccountsPayable_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInAccountsPayable_lbl1">Increase (Decrease) in Accounts Payable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInAccountsPayable" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayable_lbl1" xlink:title="label: IncreaseDecreaseInAccountsPayable to us-gaap_IncreaseDecreaseInAccountsPayable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="IncreaseDecreaseInInventories" xlink:title="IncreaseDecreaseInInventories" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInInventories" xlink:to="us-gaap_IncreaseDecreaseInInventories_lbl" xlink:title="label: IncreaseDecreaseInInventories to us-gaap_IncreaseDecreaseInInventories_lbl" />
    <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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:label="IncreaseDecreaseInOperatingCapitalAbstract" xlink:title="IncreaseDecreaseInOperatingCapitalAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl">Changes in operating assets and liabilities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" xlink:title="label: IncreaseDecreaseInOperatingCapitalAbstract to us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1">Increase (Decrease) in Operating Capital [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" xlink:title="label: IncreaseDecreaseInOperatingCapitalAbstract to us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:label="IncreaseDecreaseInOtherOperatingAssets" xlink:title="IncreaseDecreaseInOtherOperatingAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl">Other current and long-term assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherOperatingAssets" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl" xlink:title="label: IncreaseDecreaseInOtherOperatingAssets to us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1">Increase (Decrease) in Other Operating Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherOperatingAssets" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xlink:title="label: IncreaseDecreaseInOtherOperatingAssets to us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1">Increase (Decrease) in Stockholders' Equity [Roll Forward]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IntangibleAssetsFiniteLivedPolicy" xlink:to="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl" xlink:title="label: IntangibleAssetsFiniteLivedPolicy to us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IntangibleAssetsFiniteLivedPolicy" xlink:to="us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" xlink:title="label: IntangibleAssetsFiniteLivedPolicy to us-gaap_IntangibleAssetsFiniteLivedPolicy_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_InterestExpense_lbl" xml:lang="en-US" id="us-gaap_InterestExpense_lbl">Interest expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpense" xlink:to="us-gaap_InterestExpense_lbl" xlink:title="label: InterestExpense to us-gaap_InterestExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestExpense_lbl1" xml:lang="en-US" id="us-gaap_InterestExpense_lbl1">Interest Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpense" xlink:to="us-gaap_InterestExpense_lbl1" xlink:title="label: InterestExpense to us-gaap_InterestExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InterestPaidNet_lbl" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl">Interest paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestPaidNet_lbl1" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl1">Interest Paid, Excluding Capitalized Interest, Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl1" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryLineItems" xlink:label="InventoryLineItems" xlink:title="InventoryLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryLineItems_lbl" xml:lang="en-US" id="us-gaap_InventoryLineItems_lbl">Inventory [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryLineItems" xlink:to="us-gaap_InventoryLineItems_lbl" xlink:title="label: InventoryLineItems to us-gaap_InventoryLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryCurrentTable" xlink:label="InventoryCurrentTable" xlink:title="InventoryCurrentTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryCurrentTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryCurrentTable_lbl" xml:lang="en-US" id="us-gaap_InventoryCurrentTable_lbl">Inventory, Current [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryCurrentTable" xlink:to="us-gaap_InventoryCurrentTable_lbl" xlink:title="label: InventoryCurrentTable to us-gaap_InventoryCurrentTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryFinishedGoods" xlink:label="InventoryFinishedGoods" xlink:title="InventoryFinishedGoods" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryFinishedGoods_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryFinishedGoods_lbl" xml:lang="en-US" id="us-gaap_InventoryFinishedGoods_lbl">Finished goods</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryFinishedGoods" xlink:to="us-gaap_InventoryFinishedGoods_lbl" xlink:title="label: InventoryFinishedGoods to us-gaap_InventoryFinishedGoods_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryFinishedGoods_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryFinishedGoods_lbl1" xml:lang="en-US" id="us-gaap_InventoryFinishedGoods_lbl1">Inventory, Finished Goods, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryFinishedGoods" xlink:to="us-gaap_InventoryFinishedGoods_lbl1" xlink:title="label: InventoryFinishedGoods to us-gaap_InventoryFinishedGoods_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryWorkInProcess_lbl" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess_lbl">Work in process</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess_lbl" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryWorkInProcess_lbl1" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess_lbl1">Inventory, Work in Process, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess_lbl1" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryPolicyTextBlock" xlink:label="InventoryPolicyTextBlock" xlink:title="InventoryPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl">Inventory Valuation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl1">Inventory, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNet_lbl" xml:lang="en-US" id="us-gaap_InventoryNet_lbl">Inventories</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_InventoryNet_lbl1" xml:lang="en-US" id="us-gaap_InventoryNet_lbl1">Total inventory</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl1" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryNet_lbl2" xml:lang="en-US" id="us-gaap_InventoryNet_lbl2">Inventory, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl2" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNetAbstract" xlink:label="InventoryNetAbstract" xlink:title="InventoryNetAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNetAbstract_lbl" xml:lang="en-US" id="us-gaap_InventoryNetAbstract_lbl">Inventory Valuation [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract_lbl" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryNetAbstract_lbl1" xml:lang="en-US" id="us-gaap_InventoryNetAbstract_lbl1">Inventory, Net [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract_lbl1" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryRawMaterials" xlink:label="InventoryRawMaterials" xlink:title="InventoryRawMaterials" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterials_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryRawMaterials_lbl" xml:lang="en-US" id="us-gaap_InventoryRawMaterials_lbl">Raw materials</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterials" xlink:to="us-gaap_InventoryRawMaterials_lbl" xlink:title="label: InventoryRawMaterials to us-gaap_InventoryRawMaterials_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterials_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryRawMaterials_lbl1" xml:lang="en-US" id="us-gaap_InventoryRawMaterials_lbl1">Inventory, Raw Materials, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterials" xlink:to="us-gaap_InventoryRawMaterials_lbl1" xlink:title="label: InventoryRawMaterials to us-gaap_InventoryRawMaterials_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTextBlock" xlink:label="InvestmentTextBlock" xlink:title="InvestmentTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentTextBlock_lbl">Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTextBlock" xlink:to="us-gaap_InvestmentTextBlock_lbl" xlink:title="label: InvestmentTextBlock to us-gaap_InvestmentTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentTextBlock_lbl1">Investment [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTextBlock" xlink:to="us-gaap_InvestmentTextBlock_lbl1" xlink:title="label: InvestmentTextBlock to us-gaap_InvestmentTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentHoldingsLineItems_lbl" xml:lang="en-US" id="us-gaap_InvestmentHoldingsLineItems_lbl">Investment Holdings [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentHoldingsLineItems" xlink:to="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:title="label: InvestmentHoldingsLineItems to us-gaap_InvestmentHoldingsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentIncomeNet_lbl" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl">Investment income</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentIncomeNet_lbl1" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl1">Investment Income, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl1" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentPolicyTextBlock" xlink:label="InvestmentPolicyTextBlock" xlink:title="InvestmentPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl">Cash, Cash Equivalents and Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock_lbl" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl1">Investment, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentSecondaryCategorizationAxis" xlink:label="InvestmentSecondaryCategorizationAxis" xlink:title="InvestmentSecondaryCategorizationAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentSecondaryCategorizationAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentSecondaryCategorizationAxis_lbl" xml:lang="en-US" id="us-gaap_InvestmentSecondaryCategorizationAxis_lbl">Investment Secondary Categorization [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentSecondaryCategorizationAxis" xlink:to="us-gaap_InvestmentSecondaryCategorizationAxis_lbl" xlink:title="label: InvestmentSecondaryCategorizationAxis to us-gaap_InvestmentSecondaryCategorizationAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentHoldingsTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentHoldingsTable_lbl" xml:lang="en-US" id="us-gaap_InvestmentHoldingsTable_lbl">Investment Holdings [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentHoldingsTable" xlink:to="us-gaap_InvestmentHoldingsTable_lbl" xlink:title="label: InvestmentHoldingsTable to us-gaap_InvestmentHoldingsTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsBySecondaryCategorizationDomain" xlink:label="InvestmentsBySecondaryCategorizationDomain" xlink:title="InvestmentsBySecondaryCategorizationDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsBySecondaryCategorizationDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsBySecondaryCategorizationDomain_lbl" xml:lang="en-US" id="us-gaap_InvestmentsBySecondaryCategorizationDomain_lbl">Investments by Secondary Categorization [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsBySecondaryCategorizationDomain" xlink:to="us-gaap_InvestmentsBySecondaryCategorizationDomain_lbl" xlink:title="label: InvestmentsBySecondaryCategorizationDomain to us-gaap_InvestmentsBySecondaryCategorizationDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:label="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:title="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl">Contract Maturity of Available-for-Sale Securities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:to="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" xlink:title="label: InvestmentsClassifiedByContractualMaturityDateTableTextBlock to us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1">Investments Classified by Contractual Maturity Date [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:to="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" xlink:title="label: InvestmentsClassifiedByContractualMaturityDateTableTextBlock to us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsAbstract_lbl" xml:lang="en-US" id="us-gaap_InvestmentsAbstract_lbl">Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAbstract" xlink:to="us-gaap_InvestmentsAbstract_lbl" xlink:title="label: InvestmentsAbstract to us-gaap_InvestmentsAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsAllOtherInvestmentsAbstract" xlink:label="InvestmentsAllOtherInvestmentsAbstract" xlink:title="InvestmentsAllOtherInvestmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" xml:lang="en-US" id="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl">Ownership Interests in Private and Public Companies [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAllOtherInvestmentsAbstract" xlink:to="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" xlink:title="label: InvestmentsAllOtherInvestmentsAbstract to us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" xml:lang="en-US" id="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1">Investments, All Other Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAllOtherInvestmentsAbstract" xlink:to="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" xlink:title="label: InvestmentsAllOtherInvestmentsAbstract to us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeasesPolicyTextBlock" xlink:label="LesseeLeasesPolicyTextBlock" xlink:title="LesseeLeasesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl">Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl1">Lessee, Leases [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl">Lease payments over sublease term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDue to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1">Lessee, Operating Lease, Liability, to be Paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDue to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeDisclosureAbstract" xlink:label="LesseeDisclosureAbstract" xlink:title="LesseeDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract_lbl">Leases [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeDisclosureAbstract" xlink:to="us-gaap_LesseeDisclosureAbstract_lbl" xlink:title="label: LesseeDisclosureAbstract to us-gaap_LesseeDisclosureAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeDisclosureAbstract_lbl1" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract_lbl1">Lessee Disclosure [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeDisclosureAbstract" xlink:to="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:title="label: LesseeDisclosureAbstract to us-gaap_LesseeDisclosureAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="LesseeLeaseDescriptionTable" xlink:title="LesseeLeaseDescriptionTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeaseDescriptionTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeaseDescriptionTable_lbl" xml:lang="en-US" id="us-gaap_LesseeLeaseDescriptionTable_lbl">Lessee, Lease, Description [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeaseDescriptionTable" xlink:to="us-gaap_LesseeLeaseDescriptionTable_lbl" xlink:title="label: LesseeLeaseDescriptionTable to us-gaap_LesseeLeaseDescriptionTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="LesseeLeaseDescriptionLineItems" xlink:title="LesseeLeaseDescriptionLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeaseDescriptionLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeaseDescriptionLineItems_lbl" xml:lang="en-US" id="us-gaap_LesseeLeaseDescriptionLineItems_lbl">Lessee, Lease, Description [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="us-gaap_LesseeLeaseDescriptionLineItems_lbl" xlink:title="label: LesseeLeaseDescriptionLineItems to us-gaap_LesseeLeaseDescriptionLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_Liabilities_lbl" xml:lang="en-US" id="us-gaap_Liabilities_lbl">Total liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Liabilities_lbl1" xml:lang="en-US" id="us-gaap_Liabilities_lbl1">Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl1" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl">LIABILITIES AND STOCKHOLDERS' EQUITY</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1">Liabilities and Equity [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity_lbl">Total liabilities and stockholders' equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity_lbl1">Liabilities and Equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="NetCashProvidedByUsedInFinancingActivities" xlink:title="NetCashProvidedByUsedInFinancingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl">Net cash used in financing activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" xlink:title="label: NetCashProvidedByUsedInFinancingActivities to us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1">Net Cash Provided by (Used in) Financing Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInFinancingActivities to us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInFinancingActivitiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl">Financing activities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl" xlink:title="label: NetCashProvidedByUsedInFinancingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Financing Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInFinancingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl" xlink:title="label: NetCashProvidedByUsedInOperatingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract_lbl" />
    <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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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 (used in) provided by 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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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/terseLabel" xlink:title="us-gaap_NetIncomeLoss_lbl" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl">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_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/totalLabel" 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/label" xlink:title="us-gaap_NetIncomeLoss_lbl2" xml:lang="en-US" id="us-gaap_NetIncomeLoss_lbl2">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_lbl2" xlink:title="label: NetIncomeLoss to us-gaap_NetIncomeLoss_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:label="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:title="NewAccountingPronouncementsPolicyPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl">Impact of Recently Issued Accounting Standards</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:to="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" xlink:title="label: NewAccountingPronouncementsPolicyPolicyTextBlock to us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1">New Accounting Pronouncements, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:to="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" xlink:title="label: NewAccountingPronouncementsPolicyPolicyTextBlock to us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract_lbl">Other income (expense):</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract_lbl" xlink:title="label: NonoperatingIncomeExpenseAbstract to us-gaap_NonoperatingIncomeExpenseAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xml:lang="en-US" id="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1">Nonoperating Income (Expense) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" xlink:title="label: NonoperatingIncomeExpenseAbstract to us-gaap_NonoperatingIncomeExpenseAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NotesPayableFairValueDisclosure" xlink:label="NotesPayableFairValueDisclosure" xlink:title="NotesPayableFairValueDisclosure" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NotesPayableFairValueDisclosure_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NotesPayableFairValueDisclosure_lbl" xml:lang="en-US" id="us-gaap_NotesPayableFairValueDisclosure_lbl">Fair value of convertible notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NotesPayableFairValueDisclosure" xlink:to="us-gaap_NotesPayableFairValueDisclosure_lbl" xlink:title="label: NotesPayableFairValueDisclosure to us-gaap_NotesPayableFairValueDisclosure_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NotesPayableFairValueDisclosure_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NotesPayableFairValueDisclosure_lbl1" xml:lang="en-US" id="us-gaap_NotesPayableFairValueDisclosure_lbl1">Notes Payable, Fair Value Disclosure</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NotesPayableFairValueDisclosure" xlink:to="us-gaap_NotesPayableFairValueDisclosure_lbl1" xlink:title="label: NotesPayableFairValueDisclosure to us-gaap_NotesPayableFairValueDisclosure_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NumberOfOperatingSegments" xlink:label="NumberOfOperatingSegments" xlink:title="NumberOfOperatingSegments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NumberOfOperatingSegments_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NumberOfOperatingSegments_lbl" xml:lang="en-US" id="us-gaap_NumberOfOperatingSegments_lbl">Number of operating segments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfOperatingSegments" xlink:to="us-gaap_NumberOfOperatingSegments_lbl" xlink:title="label: NumberOfOperatingSegments to us-gaap_NumberOfOperatingSegments_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:label="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl">Amortization of right-of-use operating lease assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:to="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" xlink:title="label: OperatingLeaseRightOfUseAssetAmortizationExpense to us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1">Operating Lease, Right-of-Use Asset, Amortization Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:to="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xlink:title="label: OperatingLeaseRightOfUseAssetAmortizationExpense to us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="OperatingIncomeLoss" xlink:title="OperatingIncomeLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingIncomeLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_OperatingIncomeLoss_lbl" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss_lbl">Loss from operations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss_lbl" xlink:title="label: OperatingIncomeLoss to us-gaap_OperatingIncomeLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingIncomeLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingIncomeLoss_lbl1" xml:lang="en-US" id="us-gaap_OperatingIncomeLoss_lbl1">Operating Income (Loss)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss_lbl1" xlink:title="label: OperatingIncomeLoss to us-gaap_OperatingIncomeLoss_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl">Basis of Presentation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:to="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl" xlink:title="label: OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock to us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl1">Organization, Consolidation and Presentation of Financial Statements Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:to="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl1" xlink:title="label: OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock to us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract_lbl" xml:lang="en-US" id="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract_lbl">Basis of Presentation [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:to="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract_lbl" xlink:title="label: OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract to us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsCurrent" xlink:label="OtherAssetsCurrent" xlink:title="OtherAssetsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherAssetsCurrent_lbl" xml:lang="en-US" id="us-gaap_OtherAssetsCurrent_lbl">Other current assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent_lbl" xlink:title="label: OtherAssetsCurrent to us-gaap_OtherAssetsCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherAssetsCurrent_lbl1" xml:lang="en-US" id="us-gaap_OtherAssetsCurrent_lbl1">Other Assets, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent_lbl1" xlink:title="label: OtherAssetsCurrent to us-gaap_OtherAssetsCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="OtherAssetsNoncurrent" xlink:title="OtherAssetsNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherAssetsNoncurrent_lbl" xml:lang="en-US" id="us-gaap_OtherAssetsNoncurrent_lbl">Deposits and other assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsNoncurrent" xlink:to="us-gaap_OtherAssetsNoncurrent_lbl" xlink:title="label: OtherAssetsNoncurrent to us-gaap_OtherAssetsNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherAssetsNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_OtherAssetsNoncurrent_lbl1">Other Assets, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsNoncurrent" xlink:to="us-gaap_OtherAssetsNoncurrent_lbl1" xlink:title="label: OtherAssetsNoncurrent to us-gaap_OtherAssetsNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl">Currency translation adjustment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl" xlink:title="label: OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax to us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl1" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl1">Foreign currency translation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl1" xlink:title="label: OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax to us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl">Unrealized losses on debt securities, net of tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl" xlink:title="label: OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax to us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl1" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl1">OCI, Debt Securities, Available-for-Sale, Unrealized Holding Gain (Loss), before Adjustment, after Tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl1" xlink:title="label: OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax to us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherDebtSecuritiesMember" xlink:label="OtherDebtSecuritiesMember" xlink:title="OtherDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherDebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherDebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_OtherDebtSecuritiesMember_lbl">Other Municipal Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherDebtSecuritiesMember" xlink:to="us-gaap_OtherDebtSecuritiesMember_lbl" xlink:title="label: OtherDebtSecuritiesMember to us-gaap_OtherDebtSecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherDebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherDebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_OtherDebtSecuritiesMember_lbl1">Other Debt Obligations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherDebtSecuritiesMember" xlink:to="us-gaap_OtherDebtSecuritiesMember_lbl1" xlink:title="label: OtherDebtSecuritiesMember to us-gaap_OtherDebtSecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="OtherNonoperatingIncomeExpense" xlink:title="OtherNonoperatingIncomeExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherNonoperatingIncomeExpense_lbl" xml:lang="en-US" id="us-gaap_OtherNonoperatingIncomeExpense_lbl">Other income</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNonoperatingIncomeExpense" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_lbl" xlink:title="label: OtherNonoperatingIncomeExpense to us-gaap_OtherNonoperatingIncomeExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherNonoperatingIncomeExpense_lbl1" xml:lang="en-US" id="us-gaap_OtherNonoperatingIncomeExpense_lbl1">Other Nonoperating Income (Expense)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNonoperatingIncomeExpense" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_lbl1" xlink:title="label: OtherNonoperatingIncomeExpense to us-gaap_OtherNonoperatingIncomeExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:label="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:title="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl">Change in unrealized losses, net of tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:to="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl" xlink:title="label: OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent to us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForHedgeFinancingActivities" xlink:label="PaymentsForHedgeFinancingActivities" xlink:title="PaymentsForHedgeFinancingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForHedgeFinancingActivities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PaymentsForHedgeFinancingActivities_lbl" xml:lang="en-US" id="us-gaap_PaymentsForHedgeFinancingActivities_lbl">Purchase of note hedges</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForHedgeFinancingActivities" xlink:to="us-gaap_PaymentsForHedgeFinancingActivities_lbl" xlink:title="label: PaymentsForHedgeFinancingActivities to us-gaap_PaymentsForHedgeFinancingActivities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForHedgeFinancingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsForHedgeFinancingActivities_lbl1" xml:lang="en-US" id="us-gaap_PaymentsForHedgeFinancingActivities_lbl1">Payments for Hedge, Financing Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForHedgeFinancingActivities" xlink:to="us-gaap_PaymentsForHedgeFinancingActivities_lbl1" xlink:title="label: PaymentsForHedgeFinancingActivities to us-gaap_PaymentsForHedgeFinancingActivities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" xlink:title="label: PaymentsRelatedToTaxWithholdingForShareBasedCompensation to us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1">Payment, Tax Withholding, Share-based Payment Arrangement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xlink:title="label: PaymentsRelatedToTaxWithholdingForShareBasedCompensation to us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="PaymentsToAcquireAvailableForSaleSecuritiesDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl">Purchases of short-term investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xlink:title="label: PaymentsToAcquireAvailableForSaleSecuritiesDebt to us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1">Payments to Acquire Debt Securities, Available-for-sale</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xlink:title="label: PaymentsToAcquireAvailableForSaleSecuritiesDebt to us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireIntangibleAssets" xlink:label="PaymentsToAcquireIntangibleAssets" xlink:title="PaymentsToAcquireIntangibleAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireIntangibleAssets_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_PaymentsToAcquireIntangibleAssets_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireIntangibleAssets_lbl">Acquisition of licenses and other assets, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireIntangibleAssets" xlink:to="us-gaap_PaymentsToAcquireIntangibleAssets_lbl" xlink:title="label: PaymentsToAcquireIntangibleAssets to us-gaap_PaymentsToAcquireIntangibleAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1">Payments to Acquire Intangible Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireIntangibleAssets" xlink:to="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xlink:title="label: PaymentsToAcquireIntangibleAssets to us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="PaymentsToAcquirePropertyPlantAndEquipment" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl">Purchases of property, plant and equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipment" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipment to us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1">Payments to Acquire Property, Plant, and Equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipment" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipment to us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PerformanceSharesMember" xlink:label="PerformanceSharesMember" xlink:title="PerformanceSharesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PerformanceSharesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PerformanceSharesMember_lbl" xml:lang="en-US" id="us-gaap_PerformanceSharesMember_lbl">PRSUs [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PerformanceSharesMember" xlink:to="us-gaap_PerformanceSharesMember_lbl" xlink:title="label: PerformanceSharesMember to us-gaap_PerformanceSharesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PerformanceSharesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PerformanceSharesMember_lbl1" xml:lang="en-US" id="us-gaap_PerformanceSharesMember_lbl1">Performance Shares [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PerformanceSharesMember" xlink:to="us-gaap_PerformanceSharesMember_lbl1" xlink:title="label: PerformanceSharesMember to us-gaap_PerformanceSharesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfWarrants" xlink:label="ProceedsFromIssuanceOfWarrants" xlink:title="ProceedsFromIssuanceOfWarrants" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfWarrants_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromIssuanceOfWarrants_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfWarrants_lbl">Proceeds from issuance of warrants</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfWarrants" xlink:to="us-gaap_ProceedsFromIssuanceOfWarrants_lbl" xlink:title="label: ProceedsFromIssuanceOfWarrants to us-gaap_ProceedsFromIssuanceOfWarrants_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1">Proceeds from Issuance of Warrants</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfWarrants" xlink:to="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xlink:title="label: ProceedsFromIssuanceOfWarrants to us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl">Proceeds from sale of short-term investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:to="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" xlink:title="label: ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities to us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1">Proceeds from Sale and Maturity of Debt Securities, Available-for-sale</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:to="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" xlink:title="label: ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities to us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:label="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl">Proceeds from equity, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:to="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl" xlink:title="label: ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions to us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1">Proceeds, Issuance of Shares, Share-based Payment Arrangement, Including Option Exercised</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:to="us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1" xlink:title="label: ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions to us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductMember" xlink:to="us-gaap_ProductMember_lbl1" xlink:title="label: ProductMember to us-gaap_ProductMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="PropertyPlantAndEquipmentByTypeAxis" xlink:title="PropertyPlantAndEquipmentByTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl">Long-Lived Tangible Asset [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" xlink:title="label: PropertyPlantAndEquipmentByTypeAxis to us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="PropertyPlantAndEquipmentTypeDomain" xlink:title="PropertyPlantAndEquipmentTypeDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentTypeDomain_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentTypeDomain_lbl">Long-Lived Tangible Asset [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentTypeDomain" xlink:to="us-gaap_PropertyPlantAndEquipmentTypeDomain_lbl" xlink:title="label: PropertyPlantAndEquipmentTypeDomain to us-gaap_PropertyPlantAndEquipmentTypeDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="PropertyPlantAndEquipmentNet" xlink:title="PropertyPlantAndEquipmentNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentNet_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet_lbl">Property, plant and equipment, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_lbl" xlink:title="label: PropertyPlantAndEquipmentNet to us-gaap_PropertyPlantAndEquipmentNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet_lbl1">Property, Plant and Equipment, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xlink:title="label: PropertyPlantAndEquipmentNet to us-gaap_PropertyPlantAndEquipmentNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryAxis" xlink:label="PublicUtilitiesInventoryAxis" xlink:title="PublicUtilitiesInventoryAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PublicUtilitiesInventoryAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PublicUtilitiesInventoryAxis_lbl" xml:lang="en-US" id="us-gaap_PublicUtilitiesInventoryAxis_lbl">Inventory [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PublicUtilitiesInventoryAxis" xlink:to="us-gaap_PublicUtilitiesInventoryAxis_lbl" xlink:title="label: PublicUtilitiesInventoryAxis to us-gaap_PublicUtilitiesInventoryAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryTypeDomain" xlink:label="PublicUtilitiesInventoryTypeDomain" xlink:title="PublicUtilitiesInventoryTypeDomain" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RealizedInvestmentGainsLosses" xlink:label="RealizedInvestmentGainsLosses" xlink:title="RealizedInvestmentGainsLosses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RealizedInvestmentGainsLosses_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_RealizedInvestmentGainsLosses_lbl" xml:lang="en-US" id="us-gaap_RealizedInvestmentGainsLosses_lbl">Gain on investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RealizedInvestmentGainsLosses" xlink:to="us-gaap_RealizedInvestmentGainsLosses_lbl" xlink:title="label: RealizedInvestmentGainsLosses to us-gaap_RealizedInvestmentGainsLosses_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RealizedInvestmentGainsLosses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RealizedInvestmentGainsLosses_lbl1" xml:lang="en-US" id="us-gaap_RealizedInvestmentGainsLosses_lbl1">Realized Investment Gains (Losses)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RealizedInvestmentGainsLosses" xlink:to="us-gaap_RealizedInvestmentGainsLosses_lbl1" xlink:title="label: RealizedInvestmentGainsLosses to us-gaap_RealizedInvestmentGainsLosses_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ReceivablesPolicyTextBlock" xlink:label="ReceivablesPolicyTextBlock" xlink:title="ReceivablesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ReceivablesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ReceivablesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_ReceivablesPolicyTextBlock_lbl">Contracts Receivable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ReceivablesPolicyTextBlock" xlink:to="us-gaap_ReceivablesPolicyTextBlock_lbl" xlink:title="label: ReceivablesPolicyTextBlock to us-gaap_ReceivablesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ReceivablesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ReceivablesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ReceivablesPolicyTextBlock_lbl1">Receivable [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ReceivablesPolicyTextBlock" xlink:to="us-gaap_ReceivablesPolicyTextBlock_lbl1" xlink:title="label: ReceivablesPolicyTextBlock to us-gaap_ReceivablesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfConvertibleDebt" xlink:label="RepaymentsOfConvertibleDebt" xlink:title="RepaymentsOfConvertibleDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RepaymentsOfConvertibleDebt_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RepaymentsOfConvertibleDebt_lbl" xml:lang="en-US" id="us-gaap_RepaymentsOfConvertibleDebt_lbl">Repurchase of convertible notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RepaymentsOfConvertibleDebt" xlink:to="us-gaap_RepaymentsOfConvertibleDebt_lbl" xlink:title="label: RepaymentsOfConvertibleDebt to us-gaap_RepaymentsOfConvertibleDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RepaymentsOfConvertibleDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RepaymentsOfConvertibleDebt_lbl1" xml:lang="en-US" id="us-gaap_RepaymentsOfConvertibleDebt_lbl1">Repayments of Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RepaymentsOfConvertibleDebt" xlink:to="us-gaap_RepaymentsOfConvertibleDebt_lbl1" xlink:title="label: RepaymentsOfConvertibleDebt to us-gaap_RepaymentsOfConvertibleDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpensePolicy" xlink:label="ResearchAndDevelopmentExpensePolicy" xlink:title="ResearchAndDevelopmentExpensePolicy" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ResearchAndDevelopmentExpensePolicy_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ResearchAndDevelopmentExpensePolicy_lbl" xml:lang="en-US" id="us-gaap_ResearchAndDevelopmentExpensePolicy_lbl">Research and Development Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentExpensePolicy" xlink:to="us-gaap_ResearchAndDevelopmentExpensePolicy_lbl" xlink:title="label: ResearchAndDevelopmentExpensePolicy to us-gaap_ResearchAndDevelopmentExpensePolicy_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ResearchAndDevelopmentExpensePolicy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ResearchAndDevelopmentExpensePolicy_lbl1" xml:lang="en-US" id="us-gaap_ResearchAndDevelopmentExpensePolicy_lbl1">Research and Development Expense, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentExpensePolicy" xlink:to="us-gaap_ResearchAndDevelopmentExpensePolicy_lbl1" xlink:title="label: ResearchAndDevelopmentExpensePolicy to us-gaap_ResearchAndDevelopmentExpensePolicy_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="RestrictedStockUnitsRSUMember" xlink:title="RestrictedStockUnitsRSUMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestrictedStockUnitsRSUMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RestrictedStockUnitsRSUMember_lbl" xml:lang="en-US" id="us-gaap_RestrictedStockUnitsRSUMember_lbl">RSUs [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestrictedStockUnitsRSUMember" xlink:to="us-gaap_RestrictedStockUnitsRSUMember_lbl" xlink:title="label: RestrictedStockUnitsRSUMember to us-gaap_RestrictedStockUnitsRSUMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestrictedStockUnitsRSUMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestrictedStockUnitsRSUMember_lbl1" xml:lang="en-US" id="us-gaap_RestrictedStockUnitsRSUMember_lbl1">Restricted Stock Units (RSUs) [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestrictedStockUnitsRSUMember" xlink:to="us-gaap_RestrictedStockUnitsRSUMember_lbl1" xlink:title="label: RestrictedStockUnitsRSUMember to us-gaap_RestrictedStockUnitsRSUMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl">Revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl" xlink:title="label: RevenueFromContractWithCustomerExcludingAssessedTax to us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1">Revenue from Contract with Customer, Excluding Assessed Tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:title="label: RevenueFromContractWithCustomerExcludingAssessedTax to us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueRecognitionPolicyTextBlock" xlink:label="RevenueRecognitionPolicyTextBlock" xlink:title="RevenueRecognitionPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueRecognitionPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueRecognitionPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_RevenueRecognitionPolicyTextBlock_lbl">Deferred Revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueRecognitionPolicyTextBlock" xlink:to="us-gaap_RevenueRecognitionPolicyTextBlock_lbl" xlink:title="label: RevenueRecognitionPolicyTextBlock to us-gaap_RevenueRecognitionPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueRecognitionPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueRecognitionPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_RevenueRecognitionPolicyTextBlock_lbl1">Revenue [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueRecognitionPolicyTextBlock" xlink:to="us-gaap_RevenueRecognitionPolicyTextBlock_lbl1" xlink:title="label: RevenueRecognitionPolicyTextBlock to us-gaap_RevenueRecognitionPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenuesAbstract" xlink:label="RevenuesAbstract" xlink:title="RevenuesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenuesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenuesAbstract_lbl" xml:lang="en-US" id="us-gaap_RevenuesAbstract_lbl">Revenue:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenuesAbstract" xlink:to="us-gaap_RevenuesAbstract_lbl" xlink:title="label: RevenuesAbstract to us-gaap_RevenuesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenuesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenuesAbstract_lbl1" xml:lang="en-US" id="us-gaap_RevenuesAbstract_lbl1">Revenues [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenuesAbstract" xlink:to="us-gaap_RevenuesAbstract_lbl1" xlink:title="label: RevenuesAbstract to us-gaap_RevenuesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl">Expected life</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1 to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1 to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl">Award term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Expiration Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl">Vesting percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Rights, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:label="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:title="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl">Weighted-Average Assumptions for Stock Options</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:to="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl" xlink:title="label: ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock to us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1">Schedule of Share-based Payment Award, Stock Options, Valuation Assumptions [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:to="us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1" xlink:title="label: ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock to us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfInventoryCurrentTableTextBlock" xlink:label="ScheduleOfInventoryCurrentTableTextBlock" xlink:title="ScheduleOfInventoryCurrentTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl">Inventory</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfInventoryCurrentTableTextBlock" xlink:to="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl" xlink:title="label: ScheduleOfInventoryCurrentTableTextBlock to us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl1">Schedule of Inventory, Current [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfInventoryCurrentTableTextBlock" xlink:to="us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl1" xlink:title="label: ScheduleOfInventoryCurrentTableTextBlock to us-gaap_ScheduleOfInventoryCurrentTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:label="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:title="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl">Temporarily Impaired Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:to="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl" xlink:title="label: ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock to us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1">Schedule of Temporary Impairment Losses, Investments [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:to="us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1" xlink:title="label: ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock to us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:label="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:title="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl">Weighted-Average Assumptions for ESPP</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:to="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl" xlink:title="label: ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock to us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl1">Schedule of Share-based Payment Award, Employee Stock Purchase Plan, Valuation Assumptions [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:to="us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl1" xlink:title="label: ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock to us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_lbl">Schedule of Collaborative Arrangements and Non-collaborative Arrangement Transactions [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_lbl" xlink:title="label: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:label="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:title="ScheduleOfEarningsPerShareBasicByCommonClassTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_lbl">Schedule of Earnings Per Share, Basic, by Common Class, Including Two Class Method [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_lbl" xlink:title="label: ScheduleOfEarningsPerShareBasicByCommonClassTable to us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:label="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:title="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl">Schedule of Revenue by Major Customers, by Reporting Segments [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:to="us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl" xlink:title="label: ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable to us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:title="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_lbl">Schedule of Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_lbl" xlink:title="label: ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable to us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" xlink:label="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" xlink:title="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl">Stock-Based Compensation Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" xlink:to="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl" xlink:title="label: ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock to us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl1">Share-based Payment Arrangement, Expensed and Capitalized, Amount [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" xlink:to="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl1" xlink:title="label: ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock to us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:title="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_lbl">Schedule of Share-based Compensation Arrangements by Share-based Payment Award [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_lbl" xlink:title="label: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:label="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:title="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_lbl">Debt and Equity Securities, FV-NI [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:to="us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_lbl" xlink:title="label: ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems to us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:label="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:title="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_lbl">Debt Securities, Trading, and Equity Securities, FV-NI [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:to="us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_lbl" xlink:title="label: ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable to us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:label="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:title="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl" xml:lang="en-US" id="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl">Revenue from Collaborative Relationship with Biogen</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:to="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl" xlink:title="label: SchedulesOfConcentrationOfRiskByRiskFactorTextBlock to us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl1" xml:lang="en-US" id="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl1">Schedules of Concentration of Risk, by Risk Factor [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:to="us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl1" xlink:title="label: SchedulesOfConcentrationOfRiskByRiskFactorTextBlock to us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:label="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:title="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl" xml:lang="en-US" id="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl">Segment Information [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:to="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl" xlink:title="label: SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract to us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl1" xml:lang="en-US" id="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl1">Segment Reporting, Disclosure of Entity's Reportable Segments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:to="us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl1" xlink:title="label: SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract to us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentReportingPolicyPolicyTextBlock" xlink:label="SegmentReportingPolicyPolicyTextBlock" xlink:title="SegmentReportingPolicyPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl">Segment Information</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingPolicyPolicyTextBlock" xlink:to="us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl" xlink:title="label: SegmentReportingPolicyPolicyTextBlock to us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl1">Segment Reporting, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingPolicyPolicyTextBlock" xlink:to="us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl1" xlink:title="label: SegmentReportingPolicyPolicyTextBlock to us-gaap_SegmentReportingPolicyPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="SellingGeneralAndAdministrativeExpensesMember" xlink:title="SellingGeneralAndAdministrativeExpensesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl">Selling, General and Administrative Expense [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1">Selling, General and Administrative Expenses [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="SellingGeneralAndAdministrativeExpense" xlink:title="SellingGeneralAndAdministrativeExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpense_lbl" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpense_lbl">Selling, general and administrative</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpense" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpense_lbl" xlink:title="label: SellingGeneralAndAdministrativeExpense to us-gaap_SellingGeneralAndAdministrativeExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpense_lbl1" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpense_lbl1">Selling, General and Administrative Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpense" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpense_lbl1" xlink:title="label: SellingGeneralAndAdministrativeExpense to us-gaap_SellingGeneralAndAdministrativeExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl">Vesting period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheTwoMember" xlink:label="ShareBasedCompensationAwardTrancheTwoMember" xlink:title="ShareBasedCompensationAwardTrancheTwoMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheTwoMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationAwardTrancheTwoMember_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAwardTrancheTwoMember_lbl">Two-Year Period [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAwardTrancheTwoMember" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheTwoMember_lbl" xlink:title="label: ShareBasedCompensationAwardTrancheTwoMember to us-gaap_ShareBasedCompensationAwardTrancheTwoMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheOneMember" xlink:label="ShareBasedCompensationAwardTrancheOneMember" xlink:title="ShareBasedCompensationAwardTrancheOneMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl">One-Year Period [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAwardTrancheOneMember" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl" xlink:title="label: ShareBasedCompensationAwardTrancheOneMember to us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl1">Share-based Payment Arrangement, Tranche One [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAwardTrancheOneMember" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl1" xlink:title="label: ShareBasedCompensationAwardTrancheOneMember to us-gaap_ShareBasedCompensationAwardTrancheOneMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAbstract" xlink:label="ShareBasedCompensationAbstract" xlink:title="ShareBasedCompensationAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationAbstract_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAbstract_lbl">Stock-based Compensation Expense [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAbstract" xlink:to="us-gaap_ShareBasedCompensationAbstract_lbl" xlink:title="label: ShareBasedCompensationAbstract to us-gaap_ShareBasedCompensationAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationAbstract_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAbstract_lbl1">Share-based Payment Arrangement, Noncash Expense [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAbstract" xlink:to="us-gaap_ShareBasedCompensationAbstract_lbl1" xlink:title="label: ShareBasedCompensationAbstract to us-gaap_ShareBasedCompensationAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheThreeMember" xlink:label="ShareBasedCompensationAwardTrancheThreeMember" xlink:title="ShareBasedCompensationAwardTrancheThreeMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAwardTrancheThreeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationAwardTrancheThreeMember_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAwardTrancheThreeMember_lbl">Three-Year Period [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAwardTrancheThreeMember" xlink:to="us-gaap_ShareBasedCompensationAwardTrancheThreeMember_lbl" xlink:title="label: ShareBasedCompensationAwardTrancheThreeMember to us-gaap_ShareBasedCompensationAwardTrancheThreeMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="ShareBasedCompensation" xlink:title="ShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensation_lbl">Stock-based compensation expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensation" xlink:to="us-gaap_ShareBasedCompensation_lbl" xlink:title="label: ShareBasedCompensation to us-gaap_ShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensation_lbl1">Share-based Payment Arrangement, Noncash Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensation" xlink:to="us-gaap_ShareBasedCompensation_lbl1" xlink:title="label: ShareBasedCompensation to us-gaap_ShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_lbl">Share-based Compensation Arrangement by Share-based Payment Award [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedPaymentArrangementEmployeeMember" xlink:label="ShareBasedPaymentArrangementEmployeeMember" xlink:title="ShareBasedPaymentArrangementEmployeeMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl" xml:lang="en-US" id="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl">Employees [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementEmployeeMember" xlink:to="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl" xlink:title="label: ShareBasedPaymentArrangementEmployeeMember to us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1">Share-based Payment Arrangement, Employee [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementEmployeeMember" xlink:to="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xlink:title="label: ShareBasedPaymentArrangementEmployeeMember to us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl">Dividend yield</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl">RSUs and PRSUs [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Additional General Disclosures [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl">Weighted-Average Assumptions [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions and Methodology [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_lbl">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_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="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl">Volatility</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl">Weighted-average grant date fair value (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:title="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_lbl">Equity Award [Domain]</link:label>
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:label="ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:title="ShareBasedCompensationOptionAndIncentivePlansPolicy" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:label="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:title="SharesPaidForTaxWithholdingForShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" xlink:title="label: SharesPaidForTaxWithholdingForShareBasedCompensation to us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1">Share-based Payment Arrangement, Shares Withheld for Tax Withholding Obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" xlink:title="label: SharesPaidForTaxWithholdingForShareBasedCompensation to us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesIssued" xlink:label="SharesIssued" xlink:title="SharesIssued" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_SharesIssued_lbl" xml:lang="en-US" id="us-gaap_SharesIssued_lbl">Balance (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_SharesIssued_lbl1" xml:lang="en-US" id="us-gaap_SharesIssued_lbl1">Balance (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl1" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharesIssued_lbl2" xml:lang="en-US" id="us-gaap_SharesIssued_lbl2">Shares, Issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl2" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantAccountingPoliciesTextBlock" xlink:to="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" xlink:title="label: SignificantAccountingPoliciesTextBlock to us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementOfFinancialPositionAbstract" xlink:label="StatementOfFinancialPositionAbstract" xlink:title="StatementOfFinancialPositionAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfFinancialPositionAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfFinancialPositionAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfFinancialPositionAbstract_lbl">CONSOLIDATED BALANCE SHEETS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfFinancialPositionAbstract" xlink:to="us-gaap_StatementOfFinancialPositionAbstract_lbl" xlink:title="label: StatementOfFinancialPositionAbstract to us-gaap_StatementOfFinancialPositionAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:label="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:title="StatementOfIncomeAndComprehensiveIncomeAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl">CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xlink:title="label: StatementOfIncomeAndComprehensiveIncomeAbstract to us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementTable_lbl" xml:lang="en-US" id="us-gaap_StatementTable_lbl">Statement [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementTable" xlink:to="us-gaap_StatementTable_lbl" xlink:title="label: StatementTable to us-gaap_StatementTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementLineItems_lbl" xml:lang="en-US" id="us-gaap_StatementLineItems_lbl">Statement [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementLineItems" xlink:to="us-gaap_StatementLineItems_lbl" xlink:title="label: StatementLineItems to us-gaap_StatementLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementOfCashFlowsAbstract" xlink:label="StatementOfCashFlowsAbstract" xlink:title="StatementOfCashFlowsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfCashFlowsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfCashFlowsAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfCashFlowsAbstract_lbl">CONSOLIDATED STATEMENTS OF CASH FLOWS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfCashFlowsAbstract" xlink:to="us-gaap_StatementOfCashFlowsAbstract_lbl" xlink:title="label: StatementOfCashFlowsAbstract to us-gaap_StatementOfCashFlowsAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="StatementEquityComponentsAxis" xlink:title="StatementEquityComponentsAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementEquityComponentsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementEquityComponentsAxis_lbl" xml:lang="en-US" id="us-gaap_StatementEquityComponentsAxis_lbl">Equity Components [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementEquityComponentsAxis" xlink:to="us-gaap_StatementEquityComponentsAxis_lbl" xlink:title="label: StatementEquityComponentsAxis to us-gaap_StatementEquityComponentsAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementOfStockholdersEquityAbstract" xlink:label="StatementOfStockholdersEquityAbstract" xlink:title="StatementOfStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfStockholdersEquityAbstract_lbl">CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfStockholdersEquityAbstract" xlink:to="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xlink:title="label: StatementOfStockholdersEquityAbstract to us-gaap_StatementOfStockholdersEquityAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:label="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:title="StockIssuedDuringPeriodValueShareBasedCompensationGross" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl">Issuance of common stock in connection with employee stock plans</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1">Shares Issued, Value, Share-based Payment Arrangement, before Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl">Issuance of common stock in connection with employee stock plans (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1">Shares Issued, Shares, Share-based Payment Arrangement, after Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="StockholdersEquity" xlink:title="StockholdersEquity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquity_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_StockholdersEquity_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquity_lbl">Total stockholders' equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquity" xlink:to="us-gaap_StockholdersEquity_lbl" xlink:title="label: StockholdersEquity to us-gaap_StockholdersEquity_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquity_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquity_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquity_lbl1">Stockholders' Equity Attributable to Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquity" xlink:to="us-gaap_StockholdersEquity_lbl1" xlink:title="label: StockholdersEquity to us-gaap_StockholdersEquity_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:label="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl">Balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1">Balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2">Stockholders' Equity, Including Portion Attributable to Noncontrolling Interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityAbstract_lbl">Stockholders' equity:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquityAbstract_lbl" xlink:title="label: StockholdersEquityAbstract to us-gaap_StockholdersEquityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquityAbstract_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquityAbstract_lbl1">Stockholders' Equity Attributable to Parent [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquityAbstract_lbl1" xlink:title="label: StockholdersEquityAbstract to us-gaap_StockholdersEquityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SupplementalCashFlowInformationAbstract" xlink:label="SupplementalCashFlowInformationAbstract" xlink:title="SupplementalCashFlowInformationAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SupplementalCashFlowInformationAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SupplementalCashFlowInformationAbstract_lbl" xml:lang="en-US" id="us-gaap_SupplementalCashFlowInformationAbstract_lbl">Supplemental disclosures of cash flow information:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SupplementalCashFlowInformationAbstract" xlink:to="us-gaap_SupplementalCashFlowInformationAbstract_lbl" xlink:title="label: SupplementalCashFlowInformationAbstract to us-gaap_SupplementalCashFlowInformationAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SupplementalCashFlowInformationAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SupplementalCashFlowInformationAbstract_lbl1" xml:lang="en-US" id="us-gaap_SupplementalCashFlowInformationAbstract_lbl1">Supplemental Cash Flow Information [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SupplementalCashFlowInformationAbstract" xlink:to="us-gaap_SupplementalCashFlowInformationAbstract_lbl1" xlink:title="label: SupplementalCashFlowInformationAbstract to us-gaap_SupplementalCashFlowInformationAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" xlink:label="TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" xlink:title="TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" />
    <link:label xlink:type="resource" xlink:label="us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl" xml:lang="en-US" id="us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl">Unbilled SPINRAZA Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" xlink:to="us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl" xlink:title="label: TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy to us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl1" xml:lang="en-US" id="us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl1">Trade and Other Accounts Receivable, Unbilled Receivables, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" xlink:to="us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl1" xlink:title="label: TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy to us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_lbl" xml:lang="en-US" id="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_lbl">Financial Instruments [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_lbl" xlink:title="label: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_TypeOfArrangementAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_TypeOfArrangementAxis_lbl" xml:lang="en-US" id="us-gaap_TypeOfArrangementAxis_lbl">Type of Arrangement and Non-arrangement Transactions [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TypeOfArrangementAxis" xlink:to="us-gaap_TypeOfArrangementAxis_lbl" xlink:title="label: TypeOfArrangementAxis to us-gaap_TypeOfArrangementAxis_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_TypeOfArrangementAxis_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_TypeOfArrangementAxis_lbl1" xml:lang="en-US" id="us-gaap_TypeOfArrangementAxis_lbl1">Type of Arrangement and Non-arrangement Transactions [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TypeOfArrangementAxis" xlink:to="us-gaap_TypeOfArrangementAxis_lbl1" xlink:title="label: TypeOfArrangementAxis to us-gaap_TypeOfArrangementAxis_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock" xlink:label="UnrealizedGainLossOnInvestmentsTableTextBlock" xlink:title="UnrealizedGainLossOnInvestmentsTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl">Summary of Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UnrealizedGainLossOnInvestmentsTableTextBlock" xlink:to="us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl" xlink:title="label: UnrealizedGainLossOnInvestmentsTableTextBlock to us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl1">Unrealized Gain (Loss) on Investments [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UnrealizedGainLossOnInvestmentsTableTextBlock" xlink:to="us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl1" xlink:title="label: UnrealizedGainLossOnInvestmentsTableTextBlock to us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UseOfEstimates" xlink:label="UseOfEstimates" xlink:title="UseOfEstimates" />
    <link:label xlink:type="resource" xlink:label="us-gaap_UseOfEstimates_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_UseOfEstimates_lbl" xml:lang="en-US" id="us-gaap_UseOfEstimates_lbl">Use of Estimates</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UseOfEstimates" xlink:to="us-gaap_UseOfEstimates_lbl" xlink:title="label: UseOfEstimates to us-gaap_UseOfEstimates_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_UseOfEstimates_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_UseOfEstimates_lbl1" xml:lang="en-US" id="us-gaap_UseOfEstimates_lbl1">Use of Estimates, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UseOfEstimates" xlink:to="us-gaap_UseOfEstimates_lbl1" xlink:title="label: UseOfEstimates to us-gaap_UseOfEstimates_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember" xlink:label="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="USGovernmentAgenciesDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl">Debt Securities Issued by U.S. Government Agencies [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="USGovernmentAgenciesDebtSecuritiesMember" xlink:to="us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl" xlink:title="label: USGovernmentAgenciesDebtSecuritiesMember to us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl1">US Government Agencies Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="USGovernmentAgenciesDebtSecuritiesMember" xlink:to="us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl1" xlink:title="label: USGovernmentAgenciesDebtSecuritiesMember to us-gaap_USGovernmentAgenciesDebtSecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USStatesAndPoliticalSubdivisionsMember" xlink:label="USStatesAndPoliticalSubdivisionsMember" xlink:title="USStatesAndPoliticalSubdivisionsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl" xml:lang="en-US" id="us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl">Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="USStatesAndPoliticalSubdivisionsMember" xlink:to="us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl" xlink:title="label: USStatesAndPoliticalSubdivisionsMember to us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl1" xml:lang="en-US" id="us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl1">US States and Political Subdivisions Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="USStatesAndPoliticalSubdivisionsMember" xlink:to="us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl1" xlink:title="label: USStatesAndPoliticalSubdivisionsMember to us-gaap_USStatesAndPoliticalSubdivisionsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember" xlink:label="USTreasurySecuritiesMember" xlink:title="USTreasurySecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_USTreasurySecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_USTreasurySecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_USTreasurySecuritiesMember_lbl">Debt Securities Issued by the U.S. Treasury [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="USTreasurySecuritiesMember" xlink:to="us-gaap_USTreasurySecuritiesMember_lbl" xlink:title="label: USTreasurySecuritiesMember to us-gaap_USTreasurySecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_USTreasurySecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_USTreasurySecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_USTreasurySecuritiesMember_lbl1">US Treasury Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="USTreasurySecuritiesMember" xlink:to="us-gaap_USTreasurySecuritiesMember_lbl1" xlink:title="label: USTreasurySecuritiesMember to us-gaap_USTreasurySecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingAxis" xlink:label="VestingAxis" xlink:title="VestingAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_VestingAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_VestingAxis_lbl" xml:lang="en-US" id="us-gaap_VestingAxis_lbl">Vesting [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VestingAxis" xlink:to="us-gaap_VestingAxis_lbl" xlink:title="label: VestingAxis to us-gaap_VestingAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingDomain" xlink:label="VestingDomain" xlink:title="VestingDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_VestingDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_VestingDomain_lbl" xml:lang="en-US" id="us-gaap_VestingDomain_lbl">Vesting [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VestingDomain" xlink:to="us-gaap_VestingDomain_lbl" xlink:title="label: VestingDomain to us-gaap_VestingDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="WeightedAverageNumberOfDilutedSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl">Shares used in computing diluted net loss per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="WeightedAverageNumberOfSharesOutstandingBasic" xlink:title="WeightedAverageNumberOfSharesOutstandingBasic" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl">Shares used in computing basic net loss per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOutstandingBasic" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" xlink:title="label: WeightedAverageNumberOfSharesOutstandingBasic to us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_EquityMethodInvesteeNameDomain" xlink:label="EquityMethodInvesteeNameDomain" xlink:title="EquityMethodInvesteeNameDomain" />
    <link:label xlink:type="resource" xlink:label="srt_EquityMethodInvesteeNameDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_EquityMethodInvesteeNameDomain_lbl" xml:lang="en-US" id="srt_EquityMethodInvesteeNameDomain_lbl">Investment, Name [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityMethodInvesteeNameDomain" xlink:to="srt_EquityMethodInvesteeNameDomain_lbl" xlink:title="label: EquityMethodInvesteeNameDomain to srt_EquityMethodInvesteeNameDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ExecutiveOfficerMember" xlink:label="ExecutiveOfficerMember" xlink:title="ExecutiveOfficerMember" />
    <link:label xlink:type="resource" xlink:label="srt_ExecutiveOfficerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="srt_ExecutiveOfficerMember_lbl" xml:lang="en-US" id="srt_ExecutiveOfficerMember_lbl">Executive Officers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ExecutiveOfficerMember" xlink:to="srt_ExecutiveOfficerMember_lbl" xlink:title="label: ExecutiveOfficerMember to srt_ExecutiveOfficerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="srt_ExecutiveOfficerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ExecutiveOfficerMember_lbl1" xml:lang="en-US" id="srt_ExecutiveOfficerMember_lbl1">Executive Officer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ExecutiveOfficerMember" xlink:to="srt_ExecutiveOfficerMember_lbl1" xlink:title="label: ExecutiveOfficerMember to srt_ExecutiveOfficerMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:label xlink:type="resource" xlink:label="srt_MajorCustomersAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MajorCustomersAxis_lbl" xml:lang="en-US" id="srt_MajorCustomersAxis_lbl">Customer [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MajorCustomersAxis" xlink:to="srt_MajorCustomersAxis_lbl" xlink:title="label: MajorCustomersAxis to srt_MajorCustomersAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="MaximumMember" xlink:title="MaximumMember" />
    <link:label xlink:type="resource" xlink:label="srt_MaximumMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MaximumMember_lbl" xml:lang="en-US" id="srt_MaximumMember_lbl">Maximum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumMember" xlink:to="srt_MaximumMember_lbl" xlink:title="label: MaximumMember to srt_MaximumMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="MinimumMember" xlink:title="MinimumMember" />
    <link:label xlink:type="resource" xlink:label="srt_MinimumMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MinimumMember_lbl" xml:lang="en-US" id="srt_MinimumMember_lbl">Minimum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumMember" xlink:to="srt_MinimumMember_lbl" xlink:title="label: MinimumMember to srt_MinimumMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
    <link:label xlink:type="resource" xlink:label="srt_NameOfMajorCustomerDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_NameOfMajorCustomerDomain_lbl" xml:lang="en-US" id="srt_NameOfMajorCustomerDomain_lbl">Customer [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NameOfMajorCustomerDomain" xlink:to="srt_NameOfMajorCustomerDomain_lbl" xlink:title="label: NameOfMajorCustomerDomain to srt_NameOfMajorCustomerDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.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="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.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="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.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="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.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="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:label="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:title="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_lbl" xml:lang="en-US" id="srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_lbl">Investment, Name [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:to="srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_lbl" xlink:title="label: ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis to srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.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/2021q4/dei-2021q4.xsd#dei_DocumentType" xlink:label="DocumentType" xlink:title="DocumentType" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentType_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentType_lbl" xml:lang="en-US" id="dei_DocumentType_lbl">Document Type</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentType" xlink:to="dei_DocumentType_lbl" xlink:title="label: DocumentType to dei_DocumentType_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentQuarterlyReport" xlink:to="dei_DocumentQuarterlyReport_lbl" xlink:title="label: DocumentQuarterlyReport to dei_DocumentQuarterlyReport_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalPeriodFocus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalPeriodFocus_lbl" xml:lang="en-US" id="dei_DocumentFiscalPeriodFocus_lbl">Document Fiscal Period Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalPeriodFocus" xlink:to="dei_DocumentFiscalPeriodFocus_lbl" xlink:title="label: DocumentFiscalPeriodFocus to dei_DocumentFiscalPeriodFocus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCentralIndexKey_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCentralIndexKey_lbl" xml:lang="en-US" id="dei_EntityCentralIndexKey_lbl">Entity Central Index Key</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCentralIndexKey" xlink:to="dei_EntityCentralIndexKey_lbl" xlink:title="label: EntityCentralIndexKey to dei_EntityCentralIndexKey_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.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/2021q4/dei-2021q4.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityTaxIdentificationNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityTaxIdentificationNumber_lbl" xml:lang="en-US" id="dei_EntityTaxIdentificationNumber_lbl">Entity Tax Identification Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityTaxIdentificationNumber" xlink:to="dei_EntityTaxIdentificationNumber_lbl" xlink:title="label: EntityTaxIdentificationNumber to dei_EntityTaxIdentificationNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.xsd#dei_EntitySmallBusiness" xlink:label="EntitySmallBusiness" xlink:title="EntitySmallBusiness" />
    <link:label xlink:type="resource" xlink:label="dei_EntitySmallBusiness_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntitySmallBusiness_lbl" xml:lang="en-US" id="dei_EntitySmallBusiness_lbl">Entity Small Business</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntitySmallBusiness" xlink:to="dei_EntitySmallBusiness_lbl" xlink:title="label: EntitySmallBusiness to dei_EntitySmallBusiness_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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/2021q4/dei-2021q4.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="ions-20220331.xsd#ions_CallSpread" xlink:label="CallSpread" xlink:title="CallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CallSpread_lbl" xml:lang="en-US" id="ions_CallSpread_lbl">The net cash outflow from payments for hedge transactions and proceeds from the issuance of warrants. The call spread transaction was entered into to minimize the impact of potential economic dilution upon conversion of the 0.125% notes issued.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl" xlink:title="label: CallSpread to ions_CallSpread_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CallSpread_lbl1" xml:lang="en-US" id="ions_CallSpread_lbl1">Call Spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl1" xlink:title="label: CallSpread to ions_CallSpread_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CallSpread_lbl2" xml:lang="en-US" id="ions_CallSpread_lbl2">Cost of call spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl2" xlink:title="label: CallSpread to ions_CallSpread_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:label="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="DebtInstrumentConvertibleSharesSubjectToConversion" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl">The number of shares of common stock subject to conversion if the debt was converted to equity.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1">Debt Instrument, Convertible, Shares Subject to Conversion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl2" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl2">Total shares of common stock subject to conversion (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl2" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:label="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl">The computed conversion price per share of the debt instrument based on the the conversion feature embedded in the debt instrument and the impact of the purchased hedges in the call spread transaction.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1">Debt Instrument, Convertible, Conversion Price including call spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2">Effective conversion price per share with call spread (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:label="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl">The percentage of the principal amount of the notes to be purchased, plus accrued and unpaid interest, upon the occurrence of certain fundamental changes, as set forth in the indenture governing the convertible notes.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1">Debt Instrument, Convertible, Percentage of principal amount used as purchase price upon occurrence of fundamental change</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2">Percentage of principal amount used as purchase price upon occurrence of fundamental change</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleNotesDisclosureLineItems" xlink:label="ConvertibleNotesDisclosureLineItems" xlink:title="ConvertibleNotesDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleNotesDisclosureLineItems_lbl" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureLineItems_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="ConvertibleNotesDisclosureLineItems" xlink:to="ions_ConvertibleNotesDisclosureLineItems_lbl" xlink:title="label: ConvertibleNotesDisclosureLineItems to ions_ConvertibleNotesDisclosureLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleNotesDisclosureLineItems_lbl1" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureLineItems_lbl1">Convertible Notes Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ions_ConvertibleNotesDisclosureLineItems_lbl1" xlink:title="label: ConvertibleNotesDisclosureLineItems to ions_ConvertibleNotesDisclosureLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureLineItems_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleNotesDisclosureLineItems_lbl2" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureLineItems_lbl2">Convertible Notes [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ions_ConvertibleNotesDisclosureLineItems_lbl2" xlink:title="label: ConvertibleNotesDisclosureLineItems to ions_ConvertibleNotesDisclosureLineItems_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="ions_ConvertibleNotesDisclosureTable_lbl" xlink:title="label: ConvertibleNotesDisclosureTable to ions_ConvertibleNotesDisclosureTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleNotesDisclosureTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleNotesDisclosureTable_lbl1" xml:lang="en-US" id="ions_ConvertibleNotesDisclosureTable_lbl1">Convertible Notes Disclosure [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="ions_ConvertibleNotesDisclosureTable_lbl1" xlink:title="label: ConvertibleNotesDisclosureTable to ions_ConvertibleNotesDisclosureTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AmortizationPeriodForResearchAndDevelopmentExpenditures" xlink:label="AmortizationPeriodForResearchAndDevelopmentExpenditures" xlink:title="AmortizationPeriodForResearchAndDevelopmentExpenditures" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl" xml:lang="en-US" id="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl">Amortization period for research and development expenditures under Internal Revenue Code Section 174, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationPeriodForResearchAndDevelopmentExpenditures" xlink:to="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl" xlink:title="label: AmortizationPeriodForResearchAndDevelopmentExpenditures to ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl1" xml:lang="en-US" id="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl1">Amortization Period for Research and Development Expenditures</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationPeriodForResearchAndDevelopmentExpenditures" xlink:to="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl1" xlink:title="label: AmortizationPeriodForResearchAndDevelopmentExpenditures to ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl2" xml:lang="en-US" id="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl2">Amortization period for research and development expenditures under IRC Section 174</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationPeriodForResearchAndDevelopmentExpenditures" xlink:to="ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl2" xlink:title="label: AmortizationPeriodForResearchAndDevelopmentExpenditures to ions_AmortizationPeriodForResearchAndDevelopmentExpenditures_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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-20220331.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-20220331.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-20220331.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-20220331.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-20220331.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-20220331.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-20220331.xsd#ions_BiogenCollaborationsMember" xlink:label="BiogenCollaborationsMember" xlink:title="BiogenCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborationsMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl">Collaboration agreements entered into with Biogen Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborationsMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl1">Biogen Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl1" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborationsMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl2">Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl2" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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-20220331.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-20220331.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-20220331.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl">1 percent convertible senior notes due November 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl1">Convertible Senior Notes 1 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl2">1 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl3">1% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LesseeOperatingLeaseFreeRentPeriod" xlink:label="LesseeOperatingLeaseFreeRentPeriod" xlink:title="LesseeOperatingLeaseFreeRentPeriod" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseFreeRentPeriod_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseFreeRentPeriod_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseFreeRentPeriod_lbl">Period of time lessee will receive free rent under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseFreeRentPeriod" xlink:to="ions_LesseeOperatingLeaseFreeRentPeriod_lbl" xlink:title="label: LesseeOperatingLeaseFreeRentPeriod to ions_LesseeOperatingLeaseFreeRentPeriod_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseFreeRentPeriod_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseFreeRentPeriod_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseFreeRentPeriod_lbl1">Lessee, Operating Lease, Free Rent Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseFreeRentPeriod" xlink:to="ions_LesseeOperatingLeaseFreeRentPeriod_lbl1" xlink:title="label: LesseeOperatingLeaseFreeRentPeriod to ions_LesseeOperatingLeaseFreeRentPeriod_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseFreeRentPeriod_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseFreeRentPeriod_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseFreeRentPeriod_lbl2">Free rent period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseFreeRentPeriod" xlink:to="ions_LesseeOperatingLeaseFreeRentPeriod_lbl2" xlink:title="label: LesseeOperatingLeaseFreeRentPeriod to ions_LesseeOperatingLeaseFreeRentPeriod_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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-20220331.xsd#ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:label="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:title="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl">Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in October 2018 to develop IONIS-FB-L for the treatment of complement-mediated diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1">Roche Collaboration, Ionis-Fb-L for Complement-Mediated Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2">IONIS-FB-L for Complement-Mediated Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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-20220331.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-20220331.xsd#ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:label="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:title="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl">Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1">Percentage of costs associated with ongoing global Phase 3 development program paid by Collaboration Partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfMaterialComponents" xlink:label="NumberOfMaterialComponents" xlink:title="NumberOfMaterialComponents" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMaterialComponents_lbl" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl">The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMaterialComponents_lbl1" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl1">Number of material components</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl1" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMaterialComponents_lbl2" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl2">Number of material components</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl2" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AlnylamCollaborationMember" xlink:label="AlnylamCollaborationMember" xlink:title="AlnylamCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AlnylamCollaborationMember_lbl" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl">Collaboration agreement entered into with Alnylam Pharmaceuticals, Inc. in March 2004 to develop and commercialize RNAi therapeutics.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AlnylamCollaborationMember_lbl1" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl1">Alnylam Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl1" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AlnylamCollaborationMember_lbl2" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl2">Alnylam [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl2" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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-20220331.xsd#ions_BiogenCollaboration2018StrategicNeurologyMember" xlink:label="BiogenCollaboration2018StrategicNeurologyMember" xlink:title="BiogenCollaboration2018StrategicNeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl">Collaboration agreement entered into with Biogen Inc. in April 2018 to develop novel antisense drug candidates for a broad range of neurological diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2018StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl" xlink:title="label: BiogenCollaboration2018StrategicNeurologyMember to ions_BiogenCollaboration2018StrategicNeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1">Biogen Collaboration, 2018 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2018StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2018StrategicNeurologyMember to ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2">Biogen 2018 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2018StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2" xlink:title="label: BiogenCollaboration2018StrategicNeurologyMember to ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_Ion306Member" xlink:label="Ion306Member" xlink:title="Ion306Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion306Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion306Member_lbl" xml:lang="en-US" id="ions_Ion306Member_lbl">ION306 is an antisense oligonucleotide or ASO that is designed to boost production of the survival motor neuron protein, known as SMN.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion306Member" xlink:to="ions_Ion306Member_lbl" xlink:title="label: Ion306Member to ions_Ion306Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion306Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion306Member_lbl1" xml:lang="en-US" id="ions_Ion306Member_lbl1">Ion306 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion306Member" xlink:to="ions_Ion306Member_lbl1" xlink:title="label: Ion306Member to ions_Ion306Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion306Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion306Member_lbl2" xml:lang="en-US" id="ions_Ion306Member_lbl2">ION306 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion306Member" xlink:to="ions_Ion306Member_lbl2" xlink:title="label: Ion306Member to ions_Ion306Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:label="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:title="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl">Collaboration agreement entered into with Biogen Inc. in December 2017 to identify new antisense oligonucleotide drug candidates for the treatment of spinal muscular atrophy, or SMA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:to="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" xlink:title="label: BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember to ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1">Biogen Collaboration, New Antisense Medicines for Treatment of SMA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:to="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" xlink:title="label: BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember to ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2">New Antisense Medicines for the Treatment of SMA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:to="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2" xlink:title="label: BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember to ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfTargetsAdvanced" xlink:label="NumberOfTargetsAdvanced" xlink:title="NumberOfTargetsAdvanced" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargetsAdvanced_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTargetsAdvanced_lbl" xml:lang="en-US" id="ions_NumberOfTargetsAdvanced_lbl">Number of targets advanced under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTargetsAdvanced" xlink:to="ions_NumberOfTargetsAdvanced_lbl" xlink:title="label: NumberOfTargetsAdvanced to ions_NumberOfTargetsAdvanced_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargetsAdvanced_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTargetsAdvanced_lbl1" xml:lang="en-US" id="ions_NumberOfTargetsAdvanced_lbl1">Number of targets advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTargetsAdvanced" xlink:to="ions_NumberOfTargetsAdvanced_lbl1" xlink:title="label: NumberOfTargetsAdvanced to ions_NumberOfTargetsAdvanced_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargetsAdvanced_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfTargetsAdvanced_lbl2" xml:lang="en-US" id="ions_NumberOfTargetsAdvanced_lbl2">Number of targets advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTargetsAdvanced" xlink:to="ions_NumberOfTargetsAdvanced_lbl2" xlink:title="label: NumberOfTargetsAdvanced to ions_NumberOfTargetsAdvanced_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_Ion859Member" xlink:label="Ion859Member" xlink:title="Ion859Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion859Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion859Member_lbl" xml:lang="en-US" id="ions_Ion859Member_lbl">ION859 (BIIB094) is an antisense medicine designed to inhibit the production of the Leucine Rich Repeat Kinase 2, or LRRK2, protein as a potential therapy for Parkinson's disease, or PD.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion859Member" xlink:to="ions_Ion859Member_lbl" xlink:title="label: Ion859Member to ions_Ion859Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion859Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion859Member_lbl1" xml:lang="en-US" id="ions_Ion859Member_lbl1">Ion859 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion859Member" xlink:to="ions_Ion859Member_lbl1" xlink:title="label: Ion859Member to ions_Ion859Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion859Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion859Member_lbl2" xml:lang="en-US" id="ions_Ion859Member_lbl2">ION859 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion859Member" xlink:to="ions_Ion859Member_lbl2" xlink:title="label: Ion859Member to ions_Ion859Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:label="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="BiogenCollaboration2013StrategicNeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl">Collaborative agreement entered into with Biogen Inc. in September 2013 focused on applying antisense technology to advance the treatment of neurodegenerative diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1">Biogen Collaboration, 2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2">2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl3" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_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="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl3" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_UpfrontPaymentReceived" xlink:label="UpfrontPaymentReceived" xlink:title="UpfrontPaymentReceived" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontPaymentReceived_lbl" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl">The amount of upfront payments received during the period under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontPaymentReceived_lbl1" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl1">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl1" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontPaymentReceived_lbl2" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl2">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl2" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfAgreementsWithCollaborationPartner" xlink:label="NumberOfAgreementsWithCollaborationPartner" xlink:title="NumberOfAgreementsWithCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl">The number of agreements entered into with the collaboration partner.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl1">Number of agreements with collaboration partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl1" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xml:lang="en-US" id="ions_NumberOfAgreementsWithCollaborationPartner_lbl2">Number of agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfAgreementsWithCollaborationPartner" xlink:to="ions_NumberOfAgreementsWithCollaborationPartner_lbl2" xlink:title="label: NumberOfAgreementsWithCollaborationPartner to ions_NumberOfAgreementsWithCollaborationPartner_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AstrazenecaCollaborationEplontersenMember" xlink:label="AstrazenecaCollaborationEplontersenMember" xlink:title="AstrazenecaCollaborationEplontersenMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl">Collaboration agreement entered into with AstraZeneca PLC in December 2021 to develop and commercialize eplontersen. Eplontersen, formerly known as IONIS-TTR-L and AKCEA-TTR-L, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive and fatal disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl1" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl1">AstraZeneca Collaboration, Eplontersen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl1" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl2" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl2">Eplontersen Collaboration with AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl2" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_EquitySecuritiesPrivateCompaniesMember" xlink:label="EquitySecuritiesPrivateCompaniesMember" xlink:title="EquitySecuritiesPrivateCompaniesMember" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPrivateCompaniesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesPrivateCompaniesMember_lbl" xml:lang="en-US" id="ions_EquitySecuritiesPrivateCompaniesMember_lbl">Ownership interest or right to acquire or dispose of ownership interest in private corporations and other legal entities for which ownership interest is represented by shares of common or preferred stock, convertible securities, stock rights, or stock warrants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPrivateCompaniesMember" xlink:to="ions_EquitySecuritiesPrivateCompaniesMember_lbl" xlink:title="label: EquitySecuritiesPrivateCompaniesMember to ions_EquitySecuritiesPrivateCompaniesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPrivateCompaniesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquitySecuritiesPrivateCompaniesMember_lbl1" xml:lang="en-US" id="ions_EquitySecuritiesPrivateCompaniesMember_lbl1">Equity Securities, Private Companies [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPrivateCompaniesMember" xlink:to="ions_EquitySecuritiesPrivateCompaniesMember_lbl1" xlink:title="label: EquitySecuritiesPrivateCompaniesMember to ions_EquitySecuritiesPrivateCompaniesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPrivateCompaniesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquitySecuritiesPrivateCompaniesMember_lbl2" xml:lang="en-US" id="ions_EquitySecuritiesPrivateCompaniesMember_lbl2">Equity Securities in Private Companies [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPrivateCompaniesMember" xlink:to="ions_EquitySecuritiesPrivateCompaniesMember_lbl2" xlink:title="label: EquitySecuritiesPrivateCompaniesMember to ions_EquitySecuritiesPrivateCompaniesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_EquitySecuritiesPubliclyTradedCompaniesMember" xlink:label="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:title="EquitySecuritiesPubliclyTradedCompaniesMember" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" xml:lang="en-US" id="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl">Ownership interest or right to acquire or dispose of ownership interest in publicly traded corporations and other legal entities for which ownership interest is represented by shares of common or preferred stock, convertible securities, stock rights, or stock warrants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:to="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" xlink:title="label: EquitySecuritiesPubliclyTradedCompaniesMember to ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" xml:lang="en-US" id="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1">Equity Securities, Publicly Traded Companies [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:to="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" xlink:title="label: EquitySecuritiesPubliclyTradedCompaniesMember to ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2" xml:lang="en-US" id="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2">Equity Securities in Publicly Traded Company [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:to="ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2" xlink:title="label: EquitySecuritiesPubliclyTradedCompaniesMember to ions_EquitySecuritiesPubliclyTradedCompaniesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl">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).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl1">Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl2">Gross unrealized losses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl">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).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl1" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl1">Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Gain</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl2" xml:lang="en-US" id="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl2">Gross unrealized gains</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:to="ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi to ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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">Amortized 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-20220331.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-20220331.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-20220331.xsd#ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:label="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:title="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl" xml:lang="en-US" id="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl">Number of publicly-traded companies in which the entity has an equity investment included in other current assets.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:to="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl" xlink:title="label: NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets to ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl1" xml:lang="en-US" id="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl1">Number of Publicly-Traded Companies in which Entity has Equity Investment included in Other Current Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:to="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl1" xlink:title="label: NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets to ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl2" xml:lang="en-US" id="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl2">Number of publicly traded companies in which there is an investment included in other current assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:to="ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl2" xlink:title="label: NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets to ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ProqrTherapeuticsNVMember" xlink:label="ProqrTherapeuticsNVMember" xlink:title="ProqrTherapeuticsNVMember" />
    <link:label xlink:type="resource" xlink:label="ions_ProqrTherapeuticsNVMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ProqrTherapeuticsNVMember_lbl" xml:lang="en-US" id="ions_ProqrTherapeuticsNVMember_lbl">ProQR Therapeutics N.V. is a clinical stage biotech company that discovers and develops unique Ribonucleic acid (RNA) therapies for severe genetic disorders, specialized in retinal diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProqrTherapeuticsNVMember" xlink:to="ions_ProqrTherapeuticsNVMember_lbl" xlink:title="label: ProqrTherapeuticsNVMember to ions_ProqrTherapeuticsNVMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ProqrTherapeuticsNVMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ProqrTherapeuticsNVMember_lbl1" xml:lang="en-US" id="ions_ProqrTherapeuticsNVMember_lbl1">ProQR Therapeutics N.V. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProqrTherapeuticsNVMember" xlink:to="ions_ProqrTherapeuticsNVMember_lbl1" xlink:title="label: ProqrTherapeuticsNVMember to ions_ProqrTherapeuticsNVMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ProqrTherapeuticsNVMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ProqrTherapeuticsNVMember_lbl2" xml:lang="en-US" id="ions_ProqrTherapeuticsNVMember_lbl2">ProQR [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProqrTherapeuticsNVMember" xlink:to="ions_ProqrTherapeuticsNVMember_lbl2" xlink:title="label: ProqrTherapeuticsNVMember to ions_ProqrTherapeuticsNVMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ProqrTherapeuticsNVMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ProqrTherapeuticsNVMember_lbl3" xml:lang="en-US" id="ions_ProqrTherapeuticsNVMember_lbl3">ProQR Therapeutics N.V. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProqrTherapeuticsNVMember" xlink:to="ions_ProqrTherapeuticsNVMember_lbl3" xlink:title="label: ProqrTherapeuticsNVMember to ions_ProqrTherapeuticsNVMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BicycleTherapeuticsPlcMember" xlink:label="BicycleTherapeuticsPlcMember" xlink:title="BicycleTherapeuticsPlcMember" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleTherapeuticsPlcMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BicycleTherapeuticsPlcMember_lbl" xml:lang="en-US" id="ions_BicycleTherapeuticsPlcMember_lbl">Bicycle Therapeutics plc is a clinical-stage biopharmaceutical company that is pioneering a unique class of chemically synthesized medicines based on its proprietary bicyclic peptide product platform to address therapeutic needs unreachable with existing treatment modalities.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleTherapeuticsPlcMember" xlink:to="ions_BicycleTherapeuticsPlcMember_lbl" xlink:title="label: BicycleTherapeuticsPlcMember to ions_BicycleTherapeuticsPlcMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleTherapeuticsPlcMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BicycleTherapeuticsPlcMember_lbl1" xml:lang="en-US" id="ions_BicycleTherapeuticsPlcMember_lbl1">Bicycle Therapeutics plc [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleTherapeuticsPlcMember" xlink:to="ions_BicycleTherapeuticsPlcMember_lbl1" xlink:title="label: BicycleTherapeuticsPlcMember to ions_BicycleTherapeuticsPlcMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleTherapeuticsPlcMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BicycleTherapeuticsPlcMember_lbl2" xml:lang="en-US" id="ions_BicycleTherapeuticsPlcMember_lbl2">Bicycle [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleTherapeuticsPlcMember" xlink:to="ions_BicycleTherapeuticsPlcMember_lbl2" xlink:title="label: BicycleTherapeuticsPlcMember to ions_BicycleTherapeuticsPlcMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleTherapeuticsPlcMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_BicycleTherapeuticsPlcMember_lbl3" xml:lang="en-US" id="ions_BicycleTherapeuticsPlcMember_lbl3">Bicycle Therapeutics plc [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleTherapeuticsPlcMember" xlink:to="ions_BicycleTherapeuticsPlcMember_lbl3" xlink:title="label: BicycleTherapeuticsPlcMember to ions_BicycleTherapeuticsPlcMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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-20220331.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-20220331.xsd#ions_CollaborativeAgreementRevenueMember" xlink:label="CollaborativeAgreementRevenueMember" xlink:title="CollaborativeAgreementRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl">Revenue from research and development services performed under a collaborative agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl1" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl1">Collaborative Agreement Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl1" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl2" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl2">Collaborative Agreement Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl2" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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-20220331.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-20220331.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-20220331.xsd#ions_EplontersenJointDevelopmentRevenueMember" xlink:label="EplontersenJointDevelopmentRevenueMember" xlink:title="EplontersenJointDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_EplontersenJointDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EplontersenJointDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_EplontersenJointDevelopmentRevenueMember_lbl">Joint development revenue for eplontersen.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EplontersenJointDevelopmentRevenueMember" xlink:to="ions_EplontersenJointDevelopmentRevenueMember_lbl" xlink:title="label: EplontersenJointDevelopmentRevenueMember to ions_EplontersenJointDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EplontersenJointDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EplontersenJointDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_EplontersenJointDevelopmentRevenueMember_lbl1">Eplontersen Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EplontersenJointDevelopmentRevenueMember" xlink:to="ions_EplontersenJointDevelopmentRevenueMember_lbl1" xlink:title="label: EplontersenJointDevelopmentRevenueMember to ions_EplontersenJointDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EplontersenJointDevelopmentRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EplontersenJointDevelopmentRevenueMember_lbl2" xml:lang="en-US" id="ions_EplontersenJointDevelopmentRevenueMember_lbl2">Eplontersen Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EplontersenJointDevelopmentRevenueMember" xlink:to="ions_EplontersenJointDevelopmentRevenueMember_lbl2" xlink:title="label: EplontersenJointDevelopmentRevenueMember to ions_EplontersenJointDevelopmentRevenueMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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-20220331.xsd#ions_ResearchAndDevelopmentRevenueMember" xlink:label="ResearchAndDevelopmentRevenueMember" xlink:title="ResearchAndDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl">Revenue from research and development services.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl1">Research and Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl1" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl2">Research and Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl2" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl3" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl3">R&amp;D Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl3" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl">Percentage of units guaranteed to vest under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Percentage of units guaranteed to vest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2">Percentage of units guaranteed to vest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl">Number of units guaranteed to vest under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Number of units guaranteed to vest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2">Number of units guaranteed to vest (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl">Number of separate performance periods under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Number of Performance Periods</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2">Number of performance periods</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:label="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:title="ShareBasedPaymentArrangementBoardOfDirectorMember" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl">Recipient, of award granted under share-based payment arrangement, over whom grantor exercises or has right to exercise sufficient control to establish employer-employee relationship based on law of pertinent jurisdiction. Includes nonemployee director treated as employee when acting as member of board of directors, if elected by grantor's shareholders or appointed to board position to be filled by shareholder election when existing term expires.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorMember to ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1">Share-based Payment Arrangement, Board of Director [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorMember to ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2">Board of Directors [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorMember to ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:label="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:title="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl">Share-based payment arrangement granting right, subject to vesting and other restrictions, to purchase or sell certain number of shares at predetermined price for specified period of time granted on January 1, 2022 and thereafter.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember to ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1">Share-based Payment Arrangement, Options Granted on January 1, 2022 and Thereafter [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember to ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2">Stock Options Granted on January 1, 2022 and Thereafter [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember to ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:label="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:title="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl">Share-based payment arrangement granting right, subject to vesting and other restrictions, to purchase or sell certain number of shares at predetermined price for specified period of time granted prior to January 1, 2022.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member to ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1">Share-based Payment Arrangement, Options Granted Prior to January 1, 2022 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member to ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2">Stock Options Granted Prior to January 1, 2022 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member to ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchDevelopmentAndPatentExpensesMember" xlink:label="ResearchDevelopmentAndPatentExpensesMember" xlink:title="ResearchDevelopmentAndPatentExpensesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpensesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentExpensesMember_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpensesMember_lbl">Primary financial statement caption encompassing research, development and patent expenses.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpensesMember" xlink:to="ions_ResearchDevelopmentAndPatentExpensesMember_lbl" xlink:title="label: ResearchDevelopmentAndPatentExpensesMember to ions_ResearchDevelopmentAndPatentExpensesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpensesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentExpensesMember_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpensesMember_lbl1">Research, Development and Patent Expenses [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpensesMember" xlink:to="ions_ResearchDevelopmentAndPatentExpensesMember_lbl1" xlink:title="label: ResearchDevelopmentAndPatentExpensesMember to ions_ResearchDevelopmentAndPatentExpensesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpensesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ResearchDevelopmentAndPatentExpensesMember_lbl2" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpensesMember_lbl2">Research, Development and Patent Expense [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpensesMember" xlink:to="ions_ResearchDevelopmentAndPatentExpensesMember_lbl2" xlink:title="label: ResearchDevelopmentAndPatentExpensesMember to ions_ResearchDevelopmentAndPatentExpensesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_MaximumContractMaturityPeriodRange3" xlink:label="MaximumContractMaturityPeriodRange3" xlink:title="MaximumContractMaturityPeriodRange3" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl">The maximum contract maturity period for the third range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl1">Maximum contract maturity period, range 3</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl1" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl2">Maximum contract maturity period, range 3</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_MaximumContractMaturityPeriodRange2" xlink:label="MaximumContractMaturityPeriodRange2" xlink:title="MaximumContractMaturityPeriodRange2" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl">The maximum contract maturity period for the second range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2_lbl" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl1">Maximum contract maturity period, range 2</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2_lbl1" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl2">Maximum contract maturity period, range 2</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_MaximumContractMaturityPeriodRange1" xlink:label="MaximumContractMaturityPeriodRange1" xlink:title="MaximumContractMaturityPeriodRange1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl">The maximum contract maturity period for the first range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1_lbl" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl1">Maximum contract maturity period, range 1</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1_lbl1" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl2">Maximum contract maturity period, range 1</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond two years but within three and one-half years of the balance sheet date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after Two Through Three and One Half Years, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2">After two years but within three and a half years</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after One Through Two Years, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2">After one year but within two years</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl">The aggregate percentage of all available-for-sale debt securities, regardless of maturity.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1">Available-for-sale Securities, Debt Maturities, Total, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2">Total</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, within Two Years, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2">Percentage of available-for-sale securities with a maturity of less than two years</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl">The percentage of available-for-sale debt securities that mature within one year of the balance sheet date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1">Available-for-sale Securities, Debt Maturities, within One Year, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2">One year or less</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:label="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:title="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl" xml:lang="en-US" id="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl">Number of investments in privately-held companies that were revalued since the companies sold additional equity securities.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:to="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl" xlink:title="label: NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued to ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl1" xml:lang="en-US" id="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl1">Number of investments in privately-held companies that were revalued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:to="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl1" xlink:title="label: NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued to ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl2" xml:lang="en-US" id="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl2">Number of investments in privately held companies that were revalued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:to="ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl2" xlink:title="label: NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued to ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xml:lang="en-US" id="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl">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.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xlink:title="label: NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xml:lang="en-US" id="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1">Number of Publicly-Held Companies in which Entity has Equity Investment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xlink:title="label: NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xml:lang="en-US" id="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2">Number of public companies in which there is an equity ownership interest of less than 20%</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xlink:title="label: NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" xml:lang="en-US" id="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3">Number of publicly held companies in which there is an equity ownership interest of less than 20%</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" xlink:title="label: NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" xlink:title="label: NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xml:lang="en-US" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1">Number of Privately-Held Companies in which Entity has Equity Investment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" xlink:title="label: NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xml:lang="en-US" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2">Number of privately held companies in which there is an equity ownership interest of less than 20%</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" xlink:title="label: NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" xml:lang="en-US" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3">Number of private companies in which there is an equity ownership interest of less than 20%</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:to="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" xlink:title="label: NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment to ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:label="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:title="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" />
    <link:label xlink:type="resource" xlink:label="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl" xml:lang="en-US" id="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl">Dynacure is a biotechnology company developing new treatments for patients affected by serious orphan disorders. Suzhou-Ribo Life Science Co., Ltd. (Suzhou-Ribo) is a small interfering RNA (siRNA) drug development company in China, devoted to the development of innovative nucleic acid therapeutic drugs and related products. 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="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:to="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl" xlink:title="label: InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember to ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl1" xml:lang="en-US" id="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl1">Investments in Dynacure SAS, Suzhou-Ribo Life Science Co., Ltd. and Aro Biotherapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:to="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl1" xlink:title="label: InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember to ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl2" xml:lang="en-US" id="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl2">Investments in Dynacure, Suzhou-Ribo and Aro Biotherapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:to="ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl2" xlink:title="label: InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember to ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl">0 percent convertible senior notes due April 2026.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl1">Convertible Senior Notes 0 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl2">0 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl3">0% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl">0.125 percent convertible senior notes due December 2024.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl1">Convertible Senior Notes 0.125 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl2">0.125% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl3">0.125 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LongTermObligationsExcludingConvertibleDebtCurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl">Amount of long-term debt and lease obligations, excluding convertible debt, classified as current.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl" xlink:title="label: LongTermObligationsExcludingConvertibleDebtCurrent to ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1">Long-term Obligations, Excluding Convertible Debt, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1" xlink:title="label: LongTermObligationsExcludingConvertibleDebtCurrent to ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2">Current portion of long-term obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2" xlink:title="label: LongTermObligationsExcludingConvertibleDebtCurrent to ions_LongTermObligationsExcludingConvertibleDebtCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl">Amount of long-term debt and lease obligations, excluding convertible debt, classified as noncurrent.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl" xlink:title="label: LongTermObligationsExcludingConvertibleDebtNoncurrent to ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl1">Long-term Obligations Excluding Convertible Debt, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl1" xlink:title="label: LongTermObligationsExcludingConvertibleDebtNoncurrent to ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl2" xml:lang="en-US" id="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_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="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:to="ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl2" xlink:title="label: LongTermObligationsExcludingConvertibleDebtNoncurrent to ions_LongTermObligationsExcludingConvertibleDebtNoncurrent_lbl2" />
  </link:labelLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.PRE
<SEQUENCE>10
<FILENAME>ions-20220331_pre.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by EDGARfilings PROfile 8.0.0.0 Broadridge-->
<link:linkbase xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance">
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/netLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/net-2009-12-16.xsd#netLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedTotalLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedTotalLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedNetLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedNetLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedTerseLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedPeriodEndLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedPeriodEndLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedPeriodStartLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedPeriodStartLabel" />
  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedLabel" />
  <link:roleRef roleURI="http://ionispharma.com/role/ConvertibleDebtDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#ConvertibleDebtDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#CollaborativeArrangementsAndLicensingAgreementsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/IncomeTaxesDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#IncomeTaxesDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#FairValueMeasurementsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsInvestmentsTemporarilyImpairedDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsSummaryOfInvestmentsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesStockbasedCompensationExpenseDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesSegmentInformationDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesSegmentInformationDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesConvertibleDebtDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesLeasesDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesInventoryValuationDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesDeferredRevenueDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesDeferredRevenueDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesContractsReceivableDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesRevenueRecognitionDetails" />
  <link:roleRef roleURI="http://ionispharma.com/role/ConvertibleDebtTables" xlink:type="simple" xlink:href="ions-20220331.xsd#ConvertibleDebtTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsTables" xlink:type="simple" xlink:href="ions-20220331.xsd#CollaborativeArrangementsAndLicensingAgreementsTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/FairValueMeasurementsTables" xlink:type="simple" xlink:href="ions-20220331.xsd#FairValueMeasurementsTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/InvestmentsTables" xlink:type="simple" xlink:href="ions-20220331.xsd#InvestmentsTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesTables" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesTables" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPoliciesPolicies" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPoliciesPolicies" />
  <link:roleRef roleURI="http://ionispharma.com/role/BasisOfPresentationPolicies" xlink:type="simple" xlink:href="ions-20220331.xsd#BasisOfPresentationPolicies" />
  <link:roleRef roleURI="http://ionispharma.com/role/ConvertibleDebt" xlink:type="simple" xlink:href="ions-20220331.xsd#ConvertibleDebt" />
  <link:roleRef roleURI="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreements" xlink:type="simple" xlink:href="ions-20220331.xsd#CollaborativeArrangementsAndLicensingAgreements" />
  <link:roleRef roleURI="http://ionispharma.com/role/IncomeTaxes" xlink:type="simple" xlink:href="ions-20220331.xsd#IncomeTaxes" />
  <link:roleRef roleURI="http://ionispharma.com/role/FairValueMeasurements" xlink:type="simple" xlink:href="ions-20220331.xsd#FairValueMeasurements" />
  <link:roleRef roleURI="http://ionispharma.com/role/Investments" xlink:type="simple" xlink:href="ions-20220331.xsd#Investments" />
  <link:roleRef roleURI="http://ionispharma.com/role/SignificantAccountingPolicies" xlink:type="simple" xlink:href="ions-20220331.xsd#SignificantAccountingPolicies" />
  <link:roleRef roleURI="http://ionispharma.com/role/BasisOfPresentation" xlink:type="simple" xlink:href="ions-20220331.xsd#BasisOfPresentation" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfCashFlows" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfStockholdersEquity" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfComprehensiveLoss" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedStatementsOfOperations" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedBalanceSheetsParenthetical" />
  <link:roleRef roleURI="http://ionispharma.com/role/CondensedConsolidatedBalanceSheets" xlink:type="simple" xlink:href="ions-20220331.xsd#CondensedConsolidatedBalanceSheets" />
  <link:roleRef roleURI="http://ionispharma.com/role/DocumentAndEntityInformation" xlink:type="simple" xlink:href="ions-20220331.xsd#DocumentAndEntityInformation" />
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/DocumentAndEntityInformation">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_CoverAbstract" xlink:label="CoverAbstract" xlink:title="CoverAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentType" xlink:label="DocumentType" xlink:title="DocumentType" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="DocumentType" xlink:title="presentation: CoverAbstract to DocumentType" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_AmendmentFlag" xlink:label="AmendmentFlag" xlink:title="AmendmentFlag" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="AmendmentFlag" xlink:title="presentation: CoverAbstract to AmendmentFlag" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentQuarterlyReport" xlink:label="DocumentQuarterlyReport" xlink:title="DocumentQuarterlyReport" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="DocumentQuarterlyReport" xlink:title="presentation: CoverAbstract to DocumentQuarterlyReport" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentPeriodEndDate" xlink:label="DocumentPeriodEndDate" xlink:title="DocumentPeriodEndDate" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="DocumentPeriodEndDate" xlink:title="presentation: CoverAbstract to DocumentPeriodEndDate" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_CurrentFiscalYearEndDate" xlink:label="CurrentFiscalYearEndDate" xlink:title="CurrentFiscalYearEndDate" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="CurrentFiscalYearEndDate" xlink:title="presentation: CoverAbstract to CurrentFiscalYearEndDate" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentFiscalYearFocus" xlink:label="DocumentFiscalYearFocus" xlink:title="DocumentFiscalYearFocus" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="DocumentFiscalYearFocus" xlink:title="presentation: CoverAbstract to DocumentFiscalYearFocus" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="DocumentFiscalPeriodFocus" xlink:title="presentation: CoverAbstract to DocumentFiscalPeriodFocus" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_DocumentTransitionReport" xlink:label="DocumentTransitionReport" xlink:title="DocumentTransitionReport" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="DocumentTransitionReport" xlink:title="presentation: CoverAbstract to DocumentTransitionReport" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityFileNumber" xlink:title="presentation: CoverAbstract to EntityFileNumber" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityRegistrantName" xlink:title="presentation: CoverAbstract to EntityRegistrantName" order="9.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityCentralIndexKey" xlink:title="presentation: CoverAbstract to EntityCentralIndexKey" order="10.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityIncorporationStateCountryCode" xlink:label="EntityIncorporationStateCountryCode" xlink:title="EntityIncorporationStateCountryCode" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityIncorporationStateCountryCode" xlink:title="presentation: CoverAbstract to EntityIncorporationStateCountryCode" order="11.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityTaxIdentificationNumber" xlink:title="presentation: CoverAbstract to EntityTaxIdentificationNumber" order="12.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityAddressAddressLine1" xlink:label="EntityAddressAddressLine1" xlink:title="EntityAddressAddressLine1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityAddressAddressLine1" xlink:title="presentation: CoverAbstract to EntityAddressAddressLine1" order="13.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityAddressCityOrTown" xlink:label="EntityAddressCityOrTown" xlink:title="EntityAddressCityOrTown" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityAddressCityOrTown" xlink:title="presentation: CoverAbstract to EntityAddressCityOrTown" order="14.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityAddressStateOrProvince" xlink:label="EntityAddressStateOrProvince" xlink:title="EntityAddressStateOrProvince" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityAddressStateOrProvince" xlink:title="presentation: CoverAbstract to EntityAddressStateOrProvince" order="15.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityAddressPostalZipCode" xlink:label="EntityAddressPostalZipCode" xlink:title="EntityAddressPostalZipCode" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityAddressPostalZipCode" xlink:title="presentation: CoverAbstract to EntityAddressPostalZipCode" order="16.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_CityAreaCode" xlink:label="CityAreaCode" xlink:title="CityAreaCode" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="CityAreaCode" xlink:title="presentation: CoverAbstract to CityAreaCode" order="17.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_LocalPhoneNumber" xlink:label="LocalPhoneNumber" xlink:title="LocalPhoneNumber" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="LocalPhoneNumber" xlink:title="presentation: CoverAbstract to LocalPhoneNumber" order="18.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_Security12bTitle" xlink:label="Security12bTitle" xlink:title="Security12bTitle" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="Security12bTitle" xlink:title="presentation: CoverAbstract to Security12bTitle" order="19.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_TradingSymbol" xlink:label="TradingSymbol" xlink:title="TradingSymbol" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="TradingSymbol" xlink:title="presentation: CoverAbstract to TradingSymbol" order="20.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_SecurityExchangeName" xlink:label="SecurityExchangeName" xlink:title="SecurityExchangeName" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="SecurityExchangeName" xlink:title="presentation: CoverAbstract to SecurityExchangeName" order="21.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityCurrentReportingStatus" xlink:label="EntityCurrentReportingStatus" xlink:title="EntityCurrentReportingStatus" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityCurrentReportingStatus" xlink:title="presentation: CoverAbstract to EntityCurrentReportingStatus" order="22.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityInteractiveDataCurrent" xlink:label="EntityInteractiveDataCurrent" xlink:title="EntityInteractiveDataCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityInteractiveDataCurrent" xlink:title="presentation: CoverAbstract to EntityInteractiveDataCurrent" order="23.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityFilerCategory" xlink:label="EntityFilerCategory" xlink:title="EntityFilerCategory" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityFilerCategory" xlink:title="presentation: CoverAbstract to EntityFilerCategory" order="24.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntitySmallBusiness" xlink:label="EntitySmallBusiness" xlink:title="EntitySmallBusiness" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntitySmallBusiness" xlink:title="presentation: CoverAbstract to EntitySmallBusiness" order="25.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityEmergingGrowthCompany" xlink:label="EntityEmergingGrowthCompany" xlink:title="EntityEmergingGrowthCompany" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityEmergingGrowthCompany" xlink:title="presentation: CoverAbstract to EntityEmergingGrowthCompany" order="26.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityShellCompany" xlink:label="EntityShellCompany" xlink:title="EntityShellCompany" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityShellCompany" xlink:title="presentation: CoverAbstract to EntityShellCompany" order="27.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd#dei_EntityCommonStockSharesOutstanding" xlink:label="EntityCommonStockSharesOutstanding" xlink:title="EntityCommonStockSharesOutstanding" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CoverAbstract" xlink:to="EntityCommonStockSharesOutstanding" xlink:title="presentation: CoverAbstract to EntityCommonStockSharesOutstanding" order="28.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedBalanceSheets">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementOfFinancialPositionAbstract" xlink:label="StatementOfFinancialPositionAbstract" xlink:title="StatementOfFinancialPositionAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="presentation: DebtInstrumentAxis to DebtInstrumentNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementTable" xlink:to="DebtInstrumentAxis" xlink:title="presentation: StatementTable to DebtInstrumentAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsAbstract" xlink:label="AssetsAbstract" xlink:title="AssetsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrentAbstract" xlink:label="AssetsCurrentAbstract" xlink:title="AssetsCurrentAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="CashAndCashEquivalentsAtCarryingValue" xlink:title="CashAndCashEquivalentsAtCarryingValue" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsCurrentAbstract" xlink:to="CashAndCashEquivalentsAtCarryingValue" xlink:title="presentation: AssetsCurrentAbstract to CashAndCashEquivalentsAtCarryingValue" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:title="AvailableForSaleSecuritiesDebtSecuritiesCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsCurrentAbstract" xlink:to="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:title="presentation: AssetsCurrentAbstract to AvailableForSaleSecuritiesDebtSecuritiesCurrent" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerAssetNetCurrent" xlink:label="ContractWithCustomerAssetNetCurrent" xlink:title="ContractWithCustomerAssetNetCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsCurrentAbstract" xlink:to="ContractWithCustomerAssetNetCurrent" xlink:title="presentation: AssetsCurrentAbstract to ContractWithCustomerAssetNetCurrent" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsCurrentAbstract" xlink:to="InventoryNet" xlink:title="presentation: AssetsCurrentAbstract to InventoryNet" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsCurrent" xlink:label="OtherAssetsCurrent" xlink:title="OtherAssetsCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsCurrentAbstract" xlink:to="OtherAssetsCurrent" xlink:title="presentation: AssetsCurrentAbstract to OtherAssetsCurrent" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="AssetsCurrent" xlink:title="AssetsCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsCurrentAbstract" xlink:to="AssetsCurrent" xlink:title="presentation: AssetsCurrentAbstract to AssetsCurrent" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsAbstract" xlink:to="AssetsCurrentAbstract" xlink:title="presentation: AssetsAbstract to AssetsCurrentAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="PropertyPlantAndEquipmentNet" xlink:title="PropertyPlantAndEquipmentNet" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsAbstract" xlink:to="PropertyPlantAndEquipmentNet" xlink:title="presentation: AssetsAbstract to PropertyPlantAndEquipmentNet" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="FiniteLivedIntangibleAssetsNet" xlink:title="FiniteLivedIntangibleAssetsNet" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsAbstract" xlink:to="FiniteLivedIntangibleAssetsNet" xlink:title="presentation: AssetsAbstract to FiniteLivedIntangibleAssetsNet" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="OtherAssetsNoncurrent" xlink:title="OtherAssetsNoncurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsAbstract" xlink:to="OtherAssetsNoncurrent" xlink:title="presentation: AssetsAbstract to OtherAssetsNoncurrent" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Assets" xlink:label="Assets" xlink:title="Assets" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AssetsAbstract" xlink:to="Assets" xlink:title="presentation: AssetsAbstract to Assets" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="AssetsAbstract" xlink:title="presentation: StatementLineItems to AssetsAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="LiabilitiesCurrentAbstract" xlink:title="LiabilitiesCurrentAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="AccountsPayableCurrent" xlink:title="AccountsPayableCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesCurrentAbstract" xlink:to="AccountsPayableCurrent" xlink:title="presentation: LiabilitiesCurrentAbstract to AccountsPayableCurrent" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="EmployeeRelatedLiabilitiesCurrent" xlink:title="EmployeeRelatedLiabilitiesCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesCurrentAbstract" xlink:to="EmployeeRelatedLiabilitiesCurrent" xlink:title="presentation: LiabilitiesCurrentAbstract to EmployeeRelatedLiabilitiesCurrent" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="AccruedLiabilitiesCurrent" xlink:title="AccruedLiabilitiesCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesCurrentAbstract" xlink:to="AccruedLiabilitiesCurrent" xlink:title="presentation: LiabilitiesCurrentAbstract to AccruedLiabilitiesCurrent" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedIncomeTaxesCurrent" xlink:label="AccruedIncomeTaxesCurrent" xlink:title="AccruedIncomeTaxesCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesCurrentAbstract" xlink:to="AccruedIncomeTaxesCurrent" xlink:title="presentation: LiabilitiesCurrentAbstract to AccruedIncomeTaxesCurrent" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LongTermObligationsExcludingConvertibleDebtCurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesCurrentAbstract" xlink:to="LongTermObligationsExcludingConvertibleDebtCurrent" xlink:title="presentation: LiabilitiesCurrentAbstract to LongTermObligationsExcludingConvertibleDebtCurrent" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="ContractWithCustomerLiabilityCurrent" xlink:title="ContractWithCustomerLiabilityCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesCurrentAbstract" xlink:to="ContractWithCustomerLiabilityCurrent" xlink:title="presentation: LiabilitiesCurrentAbstract to ContractWithCustomerLiabilityCurrent" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesCurrentAbstract" xlink:to="LiabilitiesCurrent" xlink:title="presentation: LiabilitiesCurrentAbstract to LiabilitiesCurrent" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="LiabilitiesCurrentAbstract" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to LiabilitiesCurrentAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="ContractWithCustomerLiabilityNoncurrent" xlink:title="ContractWithCustomerLiabilityNoncurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="ContractWithCustomerLiabilityNoncurrent" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to ContractWithCustomerLiabilityNoncurrent" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleDebtNoncurrent" xlink:label="ConvertibleDebtNoncurrent" xlink:title="ConvertibleDebtNoncurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="ConvertibleDebtNoncurrent" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to ConvertibleDebtNoncurrent" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:label="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:title="LongTermObligationsExcludingConvertibleDebtNoncurrent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="LongTermObligationsExcludingConvertibleDebtNoncurrent" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to LongTermObligationsExcludingConvertibleDebtNoncurrent" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermLoansFromBank" xlink:label="LongTermLoansFromBank" xlink:title="LongTermLoansFromBank" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="LongTermLoansFromBank" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to LongTermLoansFromBank" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="Liabilities" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to Liabilities" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockValue" xlink:label="CommonStockValue" xlink:title="CommonStockValue" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="CommonStockValue" xlink:title="presentation: StockholdersEquityAbstract to CommonStockValue" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="AdditionalPaidInCapitalCommonStock" xlink:title="AdditionalPaidInCapitalCommonStock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="AdditionalPaidInCapitalCommonStock" xlink:title="presentation: StockholdersEquityAbstract to AdditionalPaidInCapitalCommonStock" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:title="AccumulatedOtherComprehensiveIncomeLossNetOfTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:title="presentation: StockholdersEquityAbstract to AccumulatedOtherComprehensiveIncomeLossNetOfTax" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="RetainedEarningsAccumulatedDeficit" xlink:title="RetainedEarningsAccumulatedDeficit" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="RetainedEarningsAccumulatedDeficit" xlink:title="presentation: StockholdersEquityAbstract to RetainedEarningsAccumulatedDeficit" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="StockholdersEquity" xlink:title="StockholdersEquity" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="StockholdersEquity" xlink:title="presentation: StockholdersEquityAbstract to StockholdersEquity" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="StockholdersEquityAbstract" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to StockholdersEquityAbstract" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="LiabilitiesAndStockholdersEquity" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to LiabilitiesAndStockholdersEquity" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="LiabilitiesAndStockholdersEquityAbstract" xlink:title="presentation: StatementLineItems to LiabilitiesAndStockholdersEquityAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementTable" xlink:to="StatementLineItems" xlink:title="presentation: StatementTable to StatementLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfFinancialPositionAbstract" xlink:to="StatementTable" xlink:title="presentation: StatementOfFinancialPositionAbstract to StatementTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementOfFinancialPositionAbstract" xlink:label="StatementOfFinancialPositionAbstract" xlink:title="StatementOfFinancialPositionAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="presentation: DebtInstrumentAxis to DebtInstrumentNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementTable" xlink:to="DebtInstrumentAxis" xlink:title="presentation: StatementTable to DebtInstrumentAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to DebtInstrumentInterestRateStatedPercentage" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare" xlink:label="CommonStockParOrStatedValuePerShare" xlink:title="CommonStockParOrStatedValuePerShare" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="CommonStockParOrStatedValuePerShare" xlink:title="presentation: StockholdersEquityAbstract to CommonStockParOrStatedValuePerShare" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesAuthorized" xlink:label="CommonStockSharesAuthorized" xlink:title="CommonStockSharesAuthorized" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="CommonStockSharesAuthorized" xlink:title="presentation: StockholdersEquityAbstract to CommonStockSharesAuthorized" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesIssued" xlink:label="CommonStockSharesIssued" xlink:title="CommonStockSharesIssued" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="CommonStockSharesIssued" xlink:title="presentation: StockholdersEquityAbstract to CommonStockSharesIssued" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesOutstanding" xlink:label="CommonStockSharesOutstanding" xlink:title="CommonStockSharesOutstanding" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StockholdersEquityAbstract" xlink:to="CommonStockSharesOutstanding" xlink:title="presentation: StockholdersEquityAbstract to CommonStockSharesOutstanding" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="StockholdersEquityAbstract" xlink:title="presentation: LiabilitiesAndStockholdersEquityAbstract to StockholdersEquityAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="LiabilitiesAndStockholdersEquityAbstract" xlink:title="presentation: StatementLineItems to LiabilitiesAndStockholdersEquityAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementTable" xlink:to="StatementLineItems" xlink:title="presentation: StatementTable to StatementLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfFinancialPositionAbstract" xlink:to="StatementTable" xlink:title="presentation: StatementOfFinancialPositionAbstract to StatementTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementAbstract" xlink:label="IncomeStatementAbstract" xlink:title="IncomeStatementAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SpinrazaRoyaltiesMember" xlink:label="SpinrazaRoyaltiesMember" xlink:title="SpinrazaRoyaltiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CommercialMember" xlink:to="SpinrazaRoyaltiesMember" xlink:title="presentation: CommercialMember to SpinrazaRoyaltiesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProductMember" xlink:label="ProductMember" xlink:title="ProductMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CommercialMember" xlink:to="ProductMember" xlink:title="presentation: CommercialMember to ProductMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LicensingAndOtherRoyaltiesMember" xlink:label="LicensingAndOtherRoyaltiesMember" xlink:title="LicensingAndOtherRoyaltiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CommercialMember" xlink:to="LicensingAndOtherRoyaltiesMember" xlink:title="presentation: CommercialMember to LicensingAndOtherRoyaltiesMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="CommercialMember" xlink:title="presentation: ProductsAndServicesDomain to CommercialMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchAndDevelopmentRevenueMember" xlink:label="ResearchAndDevelopmentRevenueMember" xlink:title="ResearchAndDevelopmentRevenueMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CollaborativeAgreementRevenueMember" xlink:label="CollaborativeAgreementRevenueMember" xlink:title="CollaborativeAgreementRevenueMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="CollaborativeAgreementRevenueMember" xlink:title="presentation: ResearchAndDevelopmentRevenueMember to CollaborativeAgreementRevenueMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_EplontersenJointDevelopmentRevenueMember" xlink:label="EplontersenJointDevelopmentRevenueMember" xlink:title="EplontersenJointDevelopmentRevenueMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="EplontersenJointDevelopmentRevenueMember" xlink:title="presentation: ResearchAndDevelopmentRevenueMember to EplontersenJointDevelopmentRevenueMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueMember" xlink:title="presentation: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductOrServiceAxis" xlink:to="ProductsAndServicesDomain" xlink:title="presentation: ProductOrServiceAxis to ProductsAndServicesDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementTable" xlink:to="ProductOrServiceAxis" xlink:title="presentation: StatementTable to ProductOrServiceAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenuesAbstract" xlink:label="RevenuesAbstract" xlink:title="RevenuesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenuesAbstract" xlink:to="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="presentation: RevenuesAbstract to RevenueFromContractWithCustomerExcludingAssessedTax" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="RevenuesAbstract" xlink:title="presentation: StatementLineItems to RevenuesAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="CostOfGoodsAndServicesSold" xlink:title="CostOfGoodsAndServicesSold" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CostsAndExpensesAbstract" xlink:to="CostOfGoodsAndServicesSold" xlink:title="presentation: CostsAndExpensesAbstract to CostOfGoodsAndServicesSold" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchDevelopmentAndPatentExpense" xlink:label="ResearchDevelopmentAndPatentExpense" xlink:title="ResearchDevelopmentAndPatentExpense" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CostsAndExpensesAbstract" xlink:to="ResearchDevelopmentAndPatentExpense" xlink:title="presentation: CostsAndExpensesAbstract to ResearchDevelopmentAndPatentExpense" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="SellingGeneralAndAdministrativeExpense" xlink:title="SellingGeneralAndAdministrativeExpense" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CostsAndExpensesAbstract" xlink:to="SellingGeneralAndAdministrativeExpense" xlink:title="presentation: CostsAndExpensesAbstract to SellingGeneralAndAdministrativeExpense" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CostsAndExpensesAbstract" xlink:to="CostsAndExpenses" xlink:title="presentation: CostsAndExpensesAbstract to CostsAndExpenses" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="CostsAndExpensesAbstract" xlink:title="presentation: StatementLineItems to CostsAndExpensesAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="OperatingIncomeLoss" xlink:title="OperatingIncomeLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="OperatingIncomeLoss" xlink:title="presentation: StatementLineItems to OperatingIncomeLoss" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="InvestmentIncomeNet" xlink:title="presentation: NonoperatingIncomeExpenseAbstract to InvestmentIncomeNet" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="InterestExpense" xlink:title="presentation: NonoperatingIncomeExpenseAbstract to InterestExpense" order="1.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnInvestments" xlink:label="GainLossOnInvestments" xlink:title="GainLossOnInvestments" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="GainLossOnInvestments" xlink:title="presentation: NonoperatingIncomeExpenseAbstract to GainLossOnInvestments" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="OtherNonoperatingIncomeExpense" xlink:title="OtherNonoperatingIncomeExpense" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NonoperatingIncomeExpenseAbstract" xlink:to="OtherNonoperatingIncomeExpense" xlink:title="presentation: NonoperatingIncomeExpenseAbstract to OtherNonoperatingIncomeExpense" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="NonoperatingIncomeExpenseAbstract" xlink:title="presentation: StatementLineItems to NonoperatingIncomeExpenseAbstract" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:title="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:title="presentation: StatementLineItems to IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="IncomeTaxExpenseBenefit" xlink:title="IncomeTaxExpenseBenefit" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="IncomeTaxExpenseBenefit" xlink:title="presentation: StatementLineItems to IncomeTaxExpenseBenefit" order="5.0" preferredLabel="http://www.xbrl.org/2009/role/negatedTerseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="NetIncomeLoss" xlink:title="presentation: StatementLineItems to NetIncomeLoss" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasic" xlink:label="EarningsPerShareBasic" xlink:title="EarningsPerShareBasic" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="EarningsPerShareBasic" xlink:title="presentation: StatementLineItems to EarningsPerShareBasic" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareDiluted" xlink:label="EarningsPerShareDiluted" xlink:title="EarningsPerShareDiluted" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="EarningsPerShareDiluted" xlink:title="presentation: StatementLineItems to EarningsPerShareDiluted" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="WeightedAverageNumberOfSharesOutstandingBasic" xlink:title="WeightedAverageNumberOfSharesOutstandingBasic" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="WeightedAverageNumberOfSharesOutstandingBasic" xlink:title="presentation: StatementLineItems to WeightedAverageNumberOfSharesOutstandingBasic" order="9.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="WeightedAverageNumberOfDilutedSharesOutstanding" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:title="presentation: StatementLineItems to WeightedAverageNumberOfDilutedSharesOutstanding" order="10.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementTable" xlink:to="StatementLineItems" xlink:title="presentation: StatementTable to StatementLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncomeStatementAbstract" xlink:to="StatementTable" xlink:title="presentation: IncomeStatementAbstract to StatementTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:label="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:title="StatementOfIncomeAndComprehensiveIncomeAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="NetIncomeLoss" xlink:title="presentation: StatementOfIncomeAndComprehensiveIncomeAbstract to NetIncomeLoss" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" xlink:title="presentation: StatementOfIncomeAndComprehensiveIncomeAbstract to OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="presentation: StatementOfIncomeAndComprehensiveIncomeAbstract to OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="ComprehensiveIncomeNetOfTax" xlink:title="ComprehensiveIncomeNetOfTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="ComprehensiveIncomeNetOfTax" xlink:title="presentation: StatementOfIncomeAndComprehensiveIncomeAbstract to ComprehensiveIncomeNetOfTax" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementOfStockholdersEquityAbstract" xlink:label="StatementOfStockholdersEquityAbstract" xlink:title="StatementOfStockholdersEquityAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="StatementEquityComponentsAxis" xlink:title="StatementEquityComponentsAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember" xlink:label="CommonStockMember" xlink:title="CommonStockMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementEquityComponentsAxis" xlink:to="CommonStockMember" xlink:title="presentation: StatementEquityComponentsAxis to CommonStockMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="AdditionalPaidInCapitalMember" xlink:title="AdditionalPaidInCapitalMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementEquityComponentsAxis" xlink:to="AdditionalPaidInCapitalMember" xlink:title="presentation: StatementEquityComponentsAxis to AdditionalPaidInCapitalMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:label="AccumulatedOtherComprehensiveIncomeMember" xlink:title="AccumulatedOtherComprehensiveIncomeMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementEquityComponentsAxis" xlink:to="AccumulatedOtherComprehensiveIncomeMember" xlink:title="presentation: StatementEquityComponentsAxis to AccumulatedOtherComprehensiveIncomeMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsMember" xlink:label="RetainedEarningsMember" xlink:title="RetainedEarningsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementEquityComponentsAxis" xlink:to="RetainedEarningsMember" xlink:title="presentation: StatementEquityComponentsAxis to RetainedEarningsMember" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="EquityComponentDomain" xlink:title="EquityComponentDomain" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementEquityComponentsAxis" xlink:to="EquityComponentDomain" xlink:title="presentation: StatementEquityComponentsAxis to EquityComponentDomain" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementTable" xlink:to="StatementEquityComponentsAxis" xlink:title="presentation: StatementTable to StatementEquityComponentsAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:label="IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="IncreaseDecreaseInStockholdersEquityRollForward" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:label="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/periodStartLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesIssued" xlink:label="SharesIssued" xlink:title="SharesIssued" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="SharesIssued" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to SharesIssued" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/periodStartLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="NetIncomeLoss" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to NetIncomeLoss" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:label="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:title="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:label="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:title="StockIssuedDuringPeriodValueShareBasedCompensationGross" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to StockIssuedDuringPeriodValueShareBasedCompensationGross" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to StockIssuedDuringPeriodSharesShareBasedCompensation" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:title="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" order="8.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:label="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:title="SharesPaidForTaxWithholdingForShareBasedCompensation" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="SharesPaidForTaxWithholdingForShareBasedCompensation" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to SharesPaidForTaxWithholdingForShareBasedCompensation" order="9.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:label="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_2" xlink:title="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_2" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" order="10.0" preferredLabel="http://www.xbrl.org/2003/role/periodEndLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesIssued" xlink:label="SharesIssued_2" xlink:title="SharesIssued" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="SharesIssued_2" xlink:title="presentation: IncreaseDecreaseInStockholdersEquityRollForward to SharesIssued" order="11.0" preferredLabel="http://www.xbrl.org/2003/role/periodEndLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementLineItems" xlink:to="IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="presentation: StatementLineItems to IncreaseDecreaseInStockholdersEquityRollForward" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementTable" xlink:to="StatementLineItems" xlink:title="presentation: StatementTable to StatementLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfStockholdersEquityAbstract" xlink:to="StatementTable" xlink:title="presentation: StatementOfStockholdersEquityAbstract to StatementTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementOfCashFlowsAbstract" xlink:label="StatementOfCashFlowsAbstract" xlink:title="StatementOfCashFlowsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="NetIncomeLoss" xlink:title="NetIncomeLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="NetIncomeLoss" xlink:title="presentation: NetCashProvidedByUsedInOperatingActivitiesAbstract to NetIncomeLoss" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Depreciation" xlink:label="Depreciation" xlink:title="Depreciation" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="Depreciation" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to Depreciation" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:label="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to OperatingLeaseRightOfUseAssetAmortizationExpense" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfIntangibleAssets" xlink:label="AmortizationOfIntangibleAssets" xlink:title="AmortizationOfIntangibleAssets" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="AmortizationOfIntangibleAssets" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to AmortizationOfIntangibleAssets" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:label="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:title="AccretionAmortizationOfDiscountsAndPremiumsInvestments" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="AccretionAmortizationOfDiscountsAndPremiumsInvestments" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to AccretionAmortizationOfDiscountsAndPremiumsInvestments" order="3.0" preferredLabel="http://www.xbrl.org/2009/role/negatedTerseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfFinancingCosts" xlink:label="AmortizationOfFinancingCosts" xlink:title="AmortizationOfFinancingCosts" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="AmortizationOfFinancingCosts" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to AmortizationOfFinancingCosts" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="ShareBasedCompensation" xlink:title="ShareBasedCompensation" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="ShareBasedCompensation" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to ShareBasedCompensation" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RealizedInvestmentGainsLosses" xlink:label="RealizedInvestmentGainsLosses" xlink:title="RealizedInvestmentGainsLosses" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="RealizedInvestmentGainsLosses" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to RealizedInvestmentGainsLosses" order="6.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnDispositionOfAssets" xlink:label="GainLossOnDispositionOfAssets" xlink:title="GainLossOnDispositionOfAssets" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="GainLossOnDispositionOfAssets" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to GainLossOnDispositionOfAssets" order="7.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ImpairmentOfIntangibleAssetsFinitelived" xlink:label="ImpairmentOfIntangibleAssetsFinitelived" xlink:title="ImpairmentOfIntangibleAssetsFinitelived" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="ImpairmentOfIntangibleAssetsFinitelived" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to ImpairmentOfIntangibleAssetsFinitelived" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:label="IncreaseDecreaseInOperatingCapitalAbstract" xlink:title="IncreaseDecreaseInOperatingCapitalAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerAsset" xlink:label="IncreaseDecreaseInContractWithCustomerAsset" xlink:title="IncreaseDecreaseInContractWithCustomerAsset" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="IncreaseDecreaseInContractWithCustomerAsset" xlink:title="presentation: IncreaseDecreaseInOperatingCapitalAbstract to IncreaseDecreaseInContractWithCustomerAsset" order="0.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="IncreaseDecreaseInInventories" xlink:title="IncreaseDecreaseInInventories" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="IncreaseDecreaseInInventories" xlink:title="presentation: IncreaseDecreaseInOperatingCapitalAbstract to IncreaseDecreaseInInventories" order="1.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:label="IncreaseDecreaseInOtherOperatingAssets" xlink:title="IncreaseDecreaseInOtherOperatingAssets" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="IncreaseDecreaseInOtherOperatingAssets" xlink:title="presentation: IncreaseDecreaseInOperatingCapitalAbstract to IncreaseDecreaseInOtherOperatingAssets" order="2.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:label="IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:title="IncreaseDecreaseInAccruedIncomeTaxesPayable" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="IncreaseDecreaseInAccruedIncomeTaxesPayable" xlink:title="presentation: IncreaseDecreaseInOperatingCapitalAbstract to IncreaseDecreaseInAccruedIncomeTaxesPayable" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="IncreaseDecreaseInAccountsPayable" xlink:title="IncreaseDecreaseInAccountsPayable" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="IncreaseDecreaseInAccountsPayable" xlink:title="presentation: IncreaseDecreaseInOperatingCapitalAbstract to IncreaseDecreaseInAccountsPayable" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:label="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="presentation: IncreaseDecreaseInOperatingCapitalAbstract to IncreaseDecreaseInOtherEmployeeRelatedLiabilities" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherCurrentLiabilities" xlink:label="IncreaseDecreaseInOtherCurrentLiabilities" xlink:title="IncreaseDecreaseInOtherCurrentLiabilities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="IncreaseDecreaseInOtherCurrentLiabilities" xlink:title="presentation: IncreaseDecreaseInOperatingCapitalAbstract to IncreaseDecreaseInOtherCurrentLiabilities" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability" xlink:label="IncreaseDecreaseInContractWithCustomerLiability" xlink:title="IncreaseDecreaseInContractWithCustomerLiability" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="IncreaseDecreaseInContractWithCustomerLiability" xlink:title="presentation: IncreaseDecreaseInOperatingCapitalAbstract to IncreaseDecreaseInContractWithCustomerLiability" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="IncreaseDecreaseInOperatingCapitalAbstract" xlink:title="presentation: AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract to IncreaseDecreaseInOperatingCapitalAbstract" order="9.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="presentation: NetCashProvidedByUsedInOperatingActivitiesAbstract to AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="NetCashProvidedByUsedInOperatingActivities" xlink:title="NetCashProvidedByUsedInOperatingActivities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:to="NetCashProvidedByUsedInOperatingActivities" xlink:title="presentation: NetCashProvidedByUsedInOperatingActivitiesAbstract to NetCashProvidedByUsedInOperatingActivities" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfCashFlowsAbstract" xlink:to="NetCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="presentation: StatementOfCashFlowsAbstract to NetCashProvidedByUsedInOperatingActivitiesAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInInvestingActivitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="PaymentsToAcquireAvailableForSaleSecuritiesDebt" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="presentation: NetCashProvidedByUsedInInvestingActivitiesAbstract to PaymentsToAcquireAvailableForSaleSecuritiesDebt" order="0.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="presentation: NetCashProvidedByUsedInInvestingActivitiesAbstract to ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="PaymentsToAcquirePropertyPlantAndEquipment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="presentation: NetCashProvidedByUsedInInvestingActivitiesAbstract to PaymentsToAcquirePropertyPlantAndEquipment" order="2.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireIntangibleAssets" xlink:label="PaymentsToAcquireIntangibleAssets" xlink:title="PaymentsToAcquireIntangibleAssets" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="PaymentsToAcquireIntangibleAssets" xlink:title="presentation: NetCashProvidedByUsedInInvestingActivitiesAbstract to PaymentsToAcquireIntangibleAssets" order="3.0" preferredLabel="http://www.xbrl.org/2009/role/negatedTerseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="NetCashProvidedByUsedInInvestingActivities" xlink:title="NetCashProvidedByUsedInInvestingActivities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:to="NetCashProvidedByUsedInInvestingActivities" xlink:title="presentation: NetCashProvidedByUsedInInvestingActivitiesAbstract to NetCashProvidedByUsedInInvestingActivities" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfCashFlowsAbstract" xlink:to="NetCashProvidedByUsedInInvestingActivitiesAbstract" xlink:title="presentation: StatementOfCashFlowsAbstract to NetCashProvidedByUsedInInvestingActivitiesAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:label="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="NetCashProvidedByUsedInFinancingActivitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:label="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="presentation: NetCashProvidedByUsedInFinancingActivitiesAbstract to ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="presentation: NetCashProvidedByUsedInFinancingActivitiesAbstract to PaymentsRelatedToTaxWithholdingForShareBasedCompensation" order="1.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="NetCashProvidedByUsedInFinancingActivities" xlink:title="NetCashProvidedByUsedInFinancingActivities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="NetCashProvidedByUsedInFinancingActivities" xlink:title="presentation: NetCashProvidedByUsedInFinancingActivitiesAbstract to NetCashProvidedByUsedInFinancingActivities" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfCashFlowsAbstract" xlink:to="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:title="presentation: StatementOfCashFlowsAbstract to NetCashProvidedByUsedInFinancingActivitiesAbstract" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents" xlink:label="EffectOfExchangeRateOnCashAndCashEquivalents" xlink:title="EffectOfExchangeRateOnCashAndCashEquivalents" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfCashFlowsAbstract" xlink:to="EffectOfExchangeRateOnCashAndCashEquivalents" xlink:title="presentation: StatementOfCashFlowsAbstract to EffectOfExchangeRateOnCashAndCashEquivalents" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfCashFlowsAbstract" xlink:to="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:title="presentation: StatementOfCashFlowsAbstract to CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfCashFlowsAbstract" xlink:to="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:title="presentation: StatementOfCashFlowsAbstract to CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/periodStartLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_2" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfCashFlowsAbstract" xlink:to="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_2" xlink:title="presentation: StatementOfCashFlowsAbstract to CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/periodEndLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SupplementalCashFlowInformationAbstract" xlink:label="SupplementalCashFlowInformationAbstract" xlink:title="SupplementalCashFlowInformationAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SupplementalCashFlowInformationAbstract" xlink:to="InterestPaidNet" xlink:title="presentation: SupplementalCashFlowInformationAbstract to InterestPaidNet" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxesPaid" xlink:label="IncomeTaxesPaid" xlink:title="IncomeTaxesPaid" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SupplementalCashFlowInformationAbstract" xlink:to="IncomeTaxesPaid" xlink:title="presentation: SupplementalCashFlowInformationAbstract to IncomeTaxesPaid" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfCashFlowsAbstract" xlink:to="SupplementalCashFlowInformationAbstract" xlink:title="presentation: StatementOfCashFlowsAbstract to SupplementalCashFlowInformationAbstract" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:label="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:title="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NonCashCapitalAndPatentExpenditures" xlink:label="NonCashCapitalAndPatentExpenditures" xlink:title="NonCashCapitalAndPatentExpenditures" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:to="NonCashCapitalAndPatentExpenditures" xlink:title="presentation: CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract to NonCashCapitalAndPatentExpenditures" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="StatementOfCashFlowsAbstract" xlink:to="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:title="presentation: StatementOfCashFlowsAbstract to CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/BasisOfPresentation">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:to="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:title="presentation: OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract to OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPolicies">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SignificantAccountingPoliciesTextBlock" xlink:label="SignificantAccountingPoliciesTextBlock" xlink:title="SignificantAccountingPoliciesTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="SignificantAccountingPoliciesTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to SignificantAccountingPoliciesTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/Investments">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentTextBlock" xlink:label="InvestmentTextBlock" xlink:title="InvestmentTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAbstract" xlink:to="InvestmentTextBlock" xlink:title="presentation: InvestmentsAbstract to InvestmentTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/FairValueMeasurements">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueDisclosuresAbstract" xlink:label="FairValueDisclosuresAbstract" xlink:title="FairValueDisclosuresAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueDisclosuresTextBlock" xlink:label="FairValueDisclosuresTextBlock" xlink:title="FairValueDisclosuresTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueDisclosuresAbstract" xlink:to="FairValueDisclosuresTextBlock" xlink:title="presentation: FairValueDisclosuresAbstract to FairValueDisclosuresTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/IncomeTaxes">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxDisclosureAbstract" xlink:label="IncomeTaxDisclosureAbstract" xlink:title="IncomeTaxDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxDisclosureTextBlock" xlink:label="IncomeTaxDisclosureTextBlock" xlink:title="IncomeTaxDisclosureTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncomeTaxDisclosureAbstract" xlink:to="IncomeTaxDisclosureTextBlock" xlink:title="presentation: IncomeTaxDisclosureAbstract to IncomeTaxDisclosureTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreements">
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementDisclosureTextBlock" xlink:label="CollaborativeArrangementDisclosureTextBlock" xlink:title="CollaborativeArrangementDisclosureTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:to="CollaborativeArrangementDisclosureTextBlock" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsAbstract to CollaborativeArrangementDisclosureTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/ConvertibleDebt">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtDisclosureAbstract" xlink:label="DebtDisclosureAbstract" xlink:title="DebtDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtDisclosureTextBlock" xlink:label="DebtDisclosureTextBlock" xlink:title="DebtDisclosureTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtDisclosureAbstract" xlink:to="DebtDisclosureTextBlock" xlink:title="presentation: DebtDisclosureAbstract to DebtDisclosureTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/BasisOfPresentationPolicies">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BasisOfAccountingPolicyPolicyTextBlock" xlink:label="BasisOfAccountingPolicyPolicyTextBlock" xlink:title="BasisOfAccountingPolicyPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:to="BasisOfAccountingPolicyPolicyTextBlock" xlink:title="presentation: OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract to BasisOfAccountingPolicyPolicyTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConsolidationPolicyTextBlock" xlink:label="ConsolidationPolicyTextBlock" xlink:title="ConsolidationPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:to="ConsolidationPolicyTextBlock" xlink:title="presentation: OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract to ConsolidationPolicyTextBlock" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesPolicies">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerPolicyTextBlock" xlink:label="RevenueFromContractWithCustomerPolicyTextBlock" xlink:title="RevenueFromContractWithCustomerPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="RevenueFromContractWithCustomerPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to RevenueFromContractWithCustomerPolicyTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ReceivablesPolicyTextBlock" xlink:label="ReceivablesPolicyTextBlock" xlink:title="ReceivablesPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ReceivablesPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to ReceivablesPolicyTextBlock" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" xlink:label="TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" xlink:title="TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" xlink:title="presentation: AccountingPoliciesAbstract to TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueRecognitionPolicyTextBlock" xlink:label="RevenueRecognitionPolicyTextBlock" xlink:title="RevenueRecognitionPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="RevenueRecognitionPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to RevenueRecognitionPolicyTextBlock" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfSalesPolicyTextBlock" xlink:label="CostOfSalesPolicyTextBlock" xlink:title="CostOfSalesPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="CostOfSalesPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to CostOfSalesPolicyTextBlock" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentPolicyTextBlock" xlink:label="InvestmentPolicyTextBlock" xlink:title="InvestmentPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="InvestmentPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to InvestmentPolicyTextBlock" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryPolicyTextBlock" xlink:label="InventoryPolicyTextBlock" xlink:title="InventoryPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="InventoryPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to InventoryPolicyTextBlock" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeasesPolicyTextBlock" xlink:label="LesseeLeasesPolicyTextBlock" xlink:title="LesseeLeasesPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="LesseeLeasesPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to LesseeLeasesPolicyTextBlock" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpensePolicy" xlink:label="ResearchAndDevelopmentExpensePolicy" xlink:title="ResearchAndDevelopmentExpensePolicy" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ResearchAndDevelopmentExpensePolicy" xlink:title="presentation: AccountingPoliciesAbstract to ResearchAndDevelopmentExpensePolicy" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IntangibleAssetsFiniteLivedPolicy" xlink:label="IntangibleAssetsFiniteLivedPolicy" xlink:title="IntangibleAssetsFiniteLivedPolicy" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="IntangibleAssetsFiniteLivedPolicy" xlink:title="presentation: AccountingPoliciesAbstract to IntangibleAssetsFiniteLivedPolicy" order="9.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxPolicyTextBlock" xlink:label="IncomeTaxPolicyTextBlock" xlink:title="IncomeTaxPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="IncomeTaxPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to IncomeTaxPolicyTextBlock" order="10.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" xlink:label="ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" xlink:title="ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock" order="11.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UseOfEstimates" xlink:label="UseOfEstimates" xlink:title="UseOfEstimates" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="UseOfEstimates" xlink:title="presentation: AccountingPoliciesAbstract to UseOfEstimates" order="12.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerSharePolicyTextBlock" xlink:label="EarningsPerSharePolicyTextBlock" xlink:title="EarningsPerSharePolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="EarningsPerSharePolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to EarningsPerSharePolicyTextBlock" order="13.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtPolicyTextBlock" xlink:label="DebtPolicyTextBlock" xlink:title="DebtPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="DebtPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to DebtPolicyTextBlock" order="14.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DerivativesPolicyTextBlock" xlink:label="DerivativesPolicyTextBlock" xlink:title="DerivativesPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="DerivativesPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to DerivativesPolicyTextBlock" order="15.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentReportingPolicyPolicyTextBlock" xlink:label="SegmentReportingPolicyPolicyTextBlock" xlink:title="SegmentReportingPolicyPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="SegmentReportingPolicyPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to SegmentReportingPolicyPolicyTextBlock" order="16.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:label="ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:title="ShareBasedCompensationOptionAndIncentivePlansPolicy" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:title="presentation: AccountingPoliciesAbstract to ShareBasedCompensationOptionAndIncentivePlansPolicy" order="17.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:label="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:title="NewAccountingPronouncementsPolicyPolicyTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to NewAccountingPronouncementsPolicyPolicyTextBlock" order="18.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesTables">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfInventoryCurrentTableTextBlock" xlink:label="ScheduleOfInventoryCurrentTableTextBlock" xlink:title="ScheduleOfInventoryCurrentTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfInventoryCurrentTableTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfInventoryCurrentTableTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:label="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:title="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:label="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:title="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" xlink:label="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" xlink:title="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsTables">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:label="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:title="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAbstract" xlink:to="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:title="presentation: InvestmentsAbstract to InvestmentsClassifiedByContractualMaturityDateTableTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock" xlink:label="UnrealizedGainLossOnInvestmentsTableTextBlock" xlink:title="UnrealizedGainLossOnInvestmentsTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAbstract" xlink:to="UnrealizedGainLossOnInvestmentsTableTextBlock" xlink:title="presentation: InvestmentsAbstract to UnrealizedGainLossOnInvestmentsTableTextBlock" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:label="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:title="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAbstract" xlink:to="ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" xlink:title="presentation: InvestmentsAbstract to ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/FairValueMeasurementsTables">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueDisclosuresAbstract" xlink:label="FairValueDisclosuresAbstract" xlink:title="FairValueDisclosuresAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock" xlink:label="FairValueAssetsMeasuredOnRecurringBasisTextBlock" xlink:title="FairValueAssetsMeasuredOnRecurringBasisTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueDisclosuresAbstract" xlink:to="FairValueAssetsMeasuredOnRecurringBasisTextBlock" xlink:title="presentation: FairValueDisclosuresAbstract to FairValueAssetsMeasuredOnRecurringBasisTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsTables">
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:label="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:title="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:to="SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsAbstract to SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/ConvertibleDebtTables">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtDisclosureAbstract" xlink:label="DebtDisclosureAbstract" xlink:title="DebtDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleNotesDisclosureTable" xlink:label="ConvertibleNotesDisclosureTable" xlink:title="ConvertibleNotesDisclosureTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="presentation: DebtInstrumentAxis to DebtInstrumentNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="DebtInstrumentAxis" xlink:title="presentation: ConvertibleNotesDisclosureTable to DebtInstrumentAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleNotesDisclosureLineItems" xlink:label="ConvertibleNotesDisclosureLineItems" xlink:title="ConvertibleNotesDisclosureLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleDebtTableTextBlock" xlink:label="ConvertibleDebtTableTextBlock" xlink:title="ConvertibleDebtTableTextBlock" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleNotesDisclosureLineItems" xlink:to="ConvertibleDebtTableTextBlock" xlink:title="presentation: ConvertibleNotesDisclosureLineItems to ConvertibleDebtTableTextBlock" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="ConvertibleNotesDisclosureLineItems" xlink:title="presentation: ConvertibleNotesDisclosureTable to ConvertibleNotesDisclosureLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtDisclosureAbstract" xlink:to="ConvertibleNotesDisclosureTable" xlink:title="presentation: DebtDisclosureAbstract to ConvertibleNotesDisclosureTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="DisaggregationOfRevenueTable" xlink:title="DisaggregationOfRevenueTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:label="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="BiogenCollaboration2013StrategicNeurologyMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to BiogenCollaboration2013StrategicNeurologyMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:label="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:title="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AlnylamCollaborationMember" xlink:label="AlnylamCollaborationMember" xlink:title="AlnylamCollaborationMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="AlnylamCollaborationMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to AlnylamCollaborationMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:label="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:title="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaboration2018StrategicNeurologyMember" xlink:label="BiogenCollaboration2018StrategicNeurologyMember" xlink:title="BiogenCollaboration2018StrategicNeurologyMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="BiogenCollaboration2018StrategicNeurologyMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to BiogenCollaboration2018StrategicNeurologyMember" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AstrazenecaCollaborationEplontersenMember" xlink:label="AstrazenecaCollaborationEplontersenMember" xlink:title="AstrazenecaCollaborationEplontersenMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="AstrazenecaCollaborationEplontersenMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to AstrazenecaCollaborationEplontersenMember" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TypeOfArrangementAxis" xlink:to="ArrangementsAndNonarrangementTransactionsMember" xlink:title="presentation: TypeOfArrangementAxis to ArrangementsAndNonarrangementTransactionsMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DisaggregationOfRevenueTable" xlink:to="TypeOfArrangementAxis" xlink:title="presentation: DisaggregationOfRevenueTable to TypeOfArrangementAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_Ion859Member" xlink:label="Ion859Member" xlink:title="Ion859Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="Ion859Member" xlink:title="presentation: ProductsAndServicesDomain to Ion859Member" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_Ion306Member" xlink:label="Ion306Member" xlink:title="Ion306Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="Ion306Member" xlink:title="presentation: ProductsAndServicesDomain to Ion306Member" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductOrServiceAxis" xlink:to="ProductsAndServicesDomain" xlink:title="presentation: ProductOrServiceAxis to ProductsAndServicesDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DisaggregationOfRevenueTable" xlink:to="ProductOrServiceAxis" xlink:title="presentation: DisaggregationOfRevenueTable to ProductOrServiceAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenIncMember" xlink:label="BiogenIncMember" xlink:title="BiogenIncMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NameOfMajorCustomerDomain" xlink:to="BiogenIncMember" xlink:title="presentation: NameOfMajorCustomerDomain to BiogenIncMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="MajorCustomersAxis" xlink:to="NameOfMajorCustomerDomain" xlink:title="presentation: MajorCustomersAxis to NameOfMajorCustomerDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DisaggregationOfRevenueTable" xlink:to="MajorCustomersAxis" xlink:title="presentation: DisaggregationOfRevenueTable to MajorCustomersAxis" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="DisaggregationOfRevenueLineItems" xlink:title="DisaggregationOfRevenueLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerAbstract" xlink:label="RevenueFromContractWithCustomerAbstract" xlink:title="RevenueFromContractWithCustomerAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to RevenueFromContractWithCustomerExcludingAssessedTax" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_UpfrontPaymentReceived" xlink:label="UpfrontPaymentReceived" xlink:title="UpfrontPaymentReceived" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="UpfrontPaymentReceived" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to UpfrontPaymentReceived" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:label="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:title="RevenueFromContractWithCustomerTransactionPriceAdditions" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="RevenueFromContractWithCustomerTransactionPriceAdditions" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to RevenueFromContractWithCustomerTransactionPriceAdditions" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfTargetsAdvanced" xlink:label="NumberOfTargetsAdvanced" xlink:title="NumberOfTargetsAdvanced" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="NumberOfTargetsAdvanced" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to NumberOfTargetsAdvanced" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfAgreementsWithCollaborationPartner" xlink:label="NumberOfAgreementsWithCollaborationPartner" xlink:title="NumberOfAgreementsWithCollaborationPartner" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="NumberOfAgreementsWithCollaborationPartner" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to NumberOfAgreementsWithCollaborationPartner" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfMaterialComponents" xlink:label="NumberOfMaterialComponents" xlink:title="NumberOfMaterialComponents" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="NumberOfMaterialComponents" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to NumberOfMaterialComponents" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:label="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:title="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_RevenueFromContractWithCustomerTransactionPrice" xlink:label="RevenueFromContractWithCustomerTransactionPrice" xlink:title="RevenueFromContractWithCustomerTransactionPrice" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="RevenueFromContractWithCustomerTransactionPrice" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to RevenueFromContractWithCustomerTransactionPrice" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:label="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:title="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:title="presentation: RevenueFromContractWithCustomerAbstract to PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DisaggregationOfRevenueLineItems" xlink:to="RevenueFromContractWithCustomerAbstract" xlink:title="presentation: DisaggregationOfRevenueLineItems to RevenueFromContractWithCustomerAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DisaggregationOfRevenueTable" xlink:to="DisaggregationOfRevenueLineItems" xlink:title="presentation: DisaggregationOfRevenueTable to DisaggregationOfRevenueLineItems" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="DisaggregationOfRevenueTable" xlink:title="presentation: AccountingPoliciesAbstract to DisaggregationOfRevenueTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractReceivablesAbstract" xlink:label="ContractReceivablesAbstract" xlink:title="ContractReceivablesAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_PeriodAfterBillingWhenPaymentIsReceived" xlink:label="PeriodAfterBillingWhenPaymentIsReceived" xlink:title="PeriodAfterBillingWhenPaymentIsReceived" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ContractReceivablesAbstract" xlink:to="PeriodAfterBillingWhenPaymentIsReceived" xlink:title="presentation: ContractReceivablesAbstract to PeriodAfterBillingWhenPaymentIsReceived" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:label="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:title="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableMember" xlink:label="AccountsReceivableMember" xlink:title="AccountsReceivableMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConcentrationRiskBenchmarkDomain" xlink:to="AccountsReceivableMember" xlink:title="presentation: ConcentrationRiskBenchmarkDomain to AccountsReceivableMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConcentrationRiskByBenchmarkAxis" xlink:to="ConcentrationRiskBenchmarkDomain" xlink:title="presentation: ConcentrationRiskByBenchmarkAxis to ConcentrationRiskBenchmarkDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:to="ConcentrationRiskByBenchmarkAxis" xlink:title="presentation: ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable to ConcentrationRiskByBenchmarkAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CreditConcentrationRiskMember" xlink:label="CreditConcentrationRiskMember" xlink:title="CreditConcentrationRiskMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConcentrationRiskTypeDomain" xlink:to="CreditConcentrationRiskMember" xlink:title="presentation: ConcentrationRiskTypeDomain to CreditConcentrationRiskMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConcentrationRiskByTypeAxis" xlink:to="ConcentrationRiskTypeDomain" xlink:title="presentation: ConcentrationRiskByTypeAxis to ConcentrationRiskTypeDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:to="ConcentrationRiskByTypeAxis" xlink:title="presentation: ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable to ConcentrationRiskByTypeAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_TwoSignificantCustomersMember" xlink:label="TwoSignificantCustomersMember" xlink:title="TwoSignificantCustomersMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="NameOfMajorCustomerDomain" xlink:to="TwoSignificantCustomersMember" xlink:title="presentation: NameOfMajorCustomerDomain to TwoSignificantCustomersMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="MajorCustomersAxis" xlink:to="NameOfMajorCustomerDomain" xlink:title="presentation: MajorCustomersAxis to NameOfMajorCustomerDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:to="MajorCustomersAxis" xlink:title="presentation: ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable to MajorCustomersAxis" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EntityWideRevenueMajorCustomerLineItems" xlink:label="EntityWideRevenueMajorCustomerLineItems" xlink:title="EntityWideRevenueMajorCustomerLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SignificantPartnersAbstract" xlink:label="SignificantPartnersAbstract" xlink:title="SignificantPartnersAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SignificantPartnersAbstract" xlink:to="ConcentrationRiskPercentage1" xlink:title="presentation: SignificantPartnersAbstract to ConcentrationRiskPercentage1" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfSignificantCustomers" xlink:label="NumberOfSignificantCustomers" xlink:title="NumberOfSignificantCustomers" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SignificantPartnersAbstract" xlink:to="NumberOfSignificantCustomers" xlink:title="presentation: SignificantPartnersAbstract to NumberOfSignificantCustomers" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EntityWideRevenueMajorCustomerLineItems" xlink:to="SignificantPartnersAbstract" xlink:title="presentation: EntityWideRevenueMajorCustomerLineItems to SignificantPartnersAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:to="EntityWideRevenueMajorCustomerLineItems" xlink:title="presentation: ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable to EntityWideRevenueMajorCustomerLineItems" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ContractReceivablesAbstract" xlink:to="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:title="presentation: ContractReceivablesAbstract to ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ContractReceivablesAbstract" xlink:title="presentation: AccountingPoliciesAbstract to ContractReceivablesAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesDeferredRevenueDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityAbstract" xlink:label="ContractWithCustomerLiabilityAbstract" xlink:title="ContractWithCustomerLiabilityAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="ContractWithCustomerLiabilityRevenueRecognized" xlink:title="ContractWithCustomerLiabilityRevenueRecognized" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ContractWithCustomerLiabilityAbstract" xlink:to="ContractWithCustomerLiabilityRevenueRecognized" xlink:title="presentation: ContractWithCustomerLiabilityAbstract to ContractWithCustomerLiabilityRevenueRecognized" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ContractWithCustomerLiabilityAbstract" xlink:title="presentation: AccountingPoliciesAbstract to ContractWithCustomerLiabilityAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:label="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:title="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:label="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:title="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" xlink:title="presentation: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="presentation: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:to="FinancialInstrumentAxis" xlink:title="presentation: ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable to FinancialInstrumentAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:label="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:title="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:label="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:title="CashCashEquivalentsAndShortTermInvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:to="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="presentation: CashCashEquivalentsAndShortTermInvestmentsAbstract to NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:to="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="presentation: CashCashEquivalentsAndShortTermInvestmentsAbstract to NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:label="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:title="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:to="NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" xlink:title="presentation: CashCashEquivalentsAndShortTermInvestmentsAbstract to NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnInvestments" xlink:label="GainLossOnInvestments" xlink:title="GainLossOnInvestments" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:to="GainLossOnInvestments" xlink:title="presentation: CashCashEquivalentsAndShortTermInvestmentsAbstract to GainLossOnInvestments" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:to="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:title="presentation: ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems to CashCashEquivalentsAndShortTermInvestmentsAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:to="ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" xlink:title="presentation: ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable to ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryCurrentTable" xlink:label="InventoryCurrentTable" xlink:title="InventoryCurrentTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryAxis" xlink:label="PublicUtilitiesInventoryAxis" xlink:title="PublicUtilitiesInventoryAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PublicUtilitiesInventoryTypeDomain" xlink:label="PublicUtilitiesInventoryTypeDomain" xlink:title="PublicUtilitiesInventoryTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ClinicalRawMaterialsMember" xlink:label="ClinicalRawMaterialsMember" xlink:title="ClinicalRawMaterialsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="PublicUtilitiesInventoryTypeDomain" xlink:to="ClinicalRawMaterialsMember" xlink:title="presentation: PublicUtilitiesInventoryTypeDomain to ClinicalRawMaterialsMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CommercialRawMaterialsMember" xlink:label="CommercialRawMaterialsMember" xlink:title="CommercialRawMaterialsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="PublicUtilitiesInventoryTypeDomain" xlink:to="CommercialRawMaterialsMember" xlink:title="presentation: PublicUtilitiesInventoryTypeDomain to CommercialRawMaterialsMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="PublicUtilitiesInventoryAxis" xlink:to="PublicUtilitiesInventoryTypeDomain" xlink:title="presentation: PublicUtilitiesInventoryAxis to PublicUtilitiesInventoryTypeDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InventoryCurrentTable" xlink:to="PublicUtilitiesInventoryAxis" xlink:title="presentation: InventoryCurrentTable to PublicUtilitiesInventoryAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryLineItems" xlink:label="InventoryLineItems" xlink:title="InventoryLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNetAbstract" xlink:label="InventoryNetAbstract" xlink:title="InventoryNetAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryRawMaterials" xlink:label="InventoryRawMaterials" xlink:title="InventoryRawMaterials" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InventoryNetAbstract" xlink:to="InventoryRawMaterials" xlink:title="presentation: InventoryNetAbstract to InventoryRawMaterials" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InventoryNetAbstract" xlink:to="InventoryWorkInProcess" xlink:title="presentation: InventoryNetAbstract to InventoryWorkInProcess" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryFinishedGoods" xlink:label="InventoryFinishedGoods" xlink:title="InventoryFinishedGoods" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InventoryNetAbstract" xlink:to="InventoryFinishedGoods" xlink:title="presentation: InventoryNetAbstract to InventoryFinishedGoods" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InventoryNetAbstract" xlink:to="InventoryNet" xlink:title="presentation: InventoryNetAbstract to InventoryNet" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InventoryLineItems" xlink:to="InventoryNetAbstract" xlink:title="presentation: InventoryLineItems to InventoryNetAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InventoryCurrentTable" xlink:to="InventoryLineItems" xlink:title="presentation: InventoryCurrentTable to InventoryLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="InventoryCurrentTable" xlink:title="presentation: AccountingPoliciesAbstract to InventoryCurrentTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="LesseeLeaseDescriptionTable" xlink:title="LesseeLeaseDescriptionTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="PropertyPlantAndEquipmentByTypeAxis" xlink:title="PropertyPlantAndEquipmentByTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain" xlink:label="PropertyPlantAndEquipmentTypeDomain" xlink:title="PropertyPlantAndEquipmentTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BuildingMember" xlink:label="BuildingMember" xlink:title="BuildingMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="PropertyPlantAndEquipmentTypeDomain" xlink:to="BuildingMember" xlink:title="presentation: PropertyPlantAndEquipmentTypeDomain to BuildingMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="PropertyPlantAndEquipmentByTypeAxis" xlink:to="PropertyPlantAndEquipmentTypeDomain" xlink:title="presentation: PropertyPlantAndEquipmentByTypeAxis to PropertyPlantAndEquipmentTypeDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeLeaseDescriptionTable" xlink:to="PropertyPlantAndEquipmentByTypeAxis" xlink:title="presentation: LesseeLeaseDescriptionTable to PropertyPlantAndEquipmentByTypeAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="LesseeLeaseDescriptionLineItems" xlink:title="LesseeLeaseDescriptionLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeDisclosureAbstract" xlink:label="LesseeDisclosureAbstract" xlink:title="LesseeDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_LesseeOperatingLeaseFreeRentPeriod" xlink:label="LesseeOperatingLeaseFreeRentPeriod" xlink:title="LesseeOperatingLeaseFreeRentPeriod" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeOperatingLeaseFreeRentPeriod" xlink:title="presentation: LesseeDisclosureAbstract to LesseeOperatingLeaseFreeRentPeriod" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDue" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeDisclosureAbstract" xlink:to="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="presentation: LesseeDisclosureAbstract to LesseeOperatingLeaseLiabilityPaymentsDue" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="LesseeDisclosureAbstract" xlink:title="presentation: LesseeLeaseDescriptionLineItems to LesseeDisclosureAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LesseeLeaseDescriptionTable" xlink:to="LesseeLeaseDescriptionLineItems" xlink:title="presentation: LesseeLeaseDescriptionTable to LesseeLeaseDescriptionLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="LesseeLeaseDescriptionTable" xlink:title="presentation: AccountingPoliciesAbstract to LesseeLeaseDescriptionTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:label="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:title="ScheduleOfEarningsPerShareBasicByCommonClassTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes1PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes1PercentMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="presentation: DebtInstrumentAxis to DebtInstrumentNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="DebtInstrumentAxis" xlink:title="presentation: ScheduleOfEarningsPerShareBasicByCommonClassTable to DebtInstrumentAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasicLineItems" xlink:label="EarningsPerShareBasicLineItems" xlink:title="EarningsPerShareBasicLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasicAbstract" xlink:label="EarningsPerShareBasicAbstract" xlink:title="EarningsPerShareBasicAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EarningsPerShareBasic" xlink:label="EarningsPerShareBasic" xlink:title="EarningsPerShareBasic" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EarningsPerShareBasicAbstract" xlink:to="EarningsPerShareBasic" xlink:title="presentation: EarningsPerShareBasicAbstract to EarningsPerShareBasic" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EarningsPerShareBasicAbstract" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="presentation: EarningsPerShareBasicAbstract to DebtInstrumentInterestRateStatedPercentage" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EarningsPerShareBasicLineItems" xlink:to="EarningsPerShareBasicAbstract" xlink:title="presentation: EarningsPerShareBasicLineItems to EarningsPerShareBasicAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:to="EarningsPerShareBasicLineItems" xlink:title="presentation: ScheduleOfEarningsPerShareBasicByCommonClassTable to EarningsPerShareBasicLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfEarningsPerShareBasicByCommonClassTable" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfEarningsPerShareBasicByCommonClassTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentTable" xlink:label="DebtInstrumentTable" xlink:title="DebtInstrumentTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="presentation: DebtInstrumentAxis to DebtInstrumentNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentTable" xlink:to="DebtInstrumentAxis" xlink:title="presentation: DebtInstrumentTable to DebtInstrumentAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="DebtInstrumentLineItems" xlink:title="DebtInstrumentLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:label="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:title="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="presentation: LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract to DebtInstrumentInterestRateStatedPercentage" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="DebtInstrumentInterestRateEffectivePercentage" xlink:title="DebtInstrumentInterestRateEffectivePercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:to="DebtInstrumentInterestRateEffectivePercentage" xlink:title="presentation: LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract to DebtInstrumentInterestRateEffectivePercentage" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentLineItems" xlink:to="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:title="presentation: DebtInstrumentLineItems to LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentTable" xlink:to="DebtInstrumentLineItems" xlink:title="presentation: DebtInstrumentTable to DebtInstrumentLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="DebtInstrumentTable" xlink:title="presentation: AccountingPoliciesAbstract to DebtInstrumentTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesSegmentInformationDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:label="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:title="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NumberOfOperatingSegments" xlink:label="NumberOfOperatingSegments" xlink:title="NumberOfOperatingSegments" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:to="NumberOfOperatingSegments" xlink:title="presentation: SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract to NumberOfOperatingSegments" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" xlink:title="presentation: AccountingPoliciesAbstract to SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountingPoliciesAbstract" xlink:label="AccountingPoliciesAbstract" xlink:title="AccountingPoliciesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:title="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="AwardTypeAxis" xlink:title="AwardTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:title="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="EmployeeStockOptionMember" xlink:title="EmployeeStockOptionMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:label="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:title="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EmployeeStockOptionMember" xlink:to="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:title="presentation: EmployeeStockOptionMember to ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:label="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:title="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EmployeeStockOptionMember" xlink:to="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:title="presentation: EmployeeStockOptionMember to ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="EmployeeStockOptionMember" xlink:title="presentation: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to EmployeeStockOptionMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockMember" xlink:label="EmployeeStockMember" xlink:title="EmployeeStockMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="EmployeeStockMember" xlink:title="presentation: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to EmployeeStockMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockUnitsRSUMember" xlink:label="RestrictedStockUnitsRSUMember" xlink:title="RestrictedStockUnitsRSUMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="RestrictedStockUnitsRSUMember" xlink:title="presentation: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to RestrictedStockUnitsRSUMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PerformanceSharesMember" xlink:label="PerformanceSharesMember" xlink:title="PerformanceSharesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="PerformanceSharesMember" xlink:title="presentation: ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain to PerformanceSharesMember" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AwardTypeAxis" xlink:to="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:title="presentation: AwardTypeAxis to ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="AwardTypeAxis" xlink:title="presentation: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to AwardTypeAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GranteeStatusAxis" xlink:label="GranteeStatusAxis" xlink:title="GranteeStatusAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GranteeStatusDomain" xlink:label="GranteeStatusDomain" xlink:title="GranteeStatusDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:label="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:title="ShareBasedPaymentArrangementBoardOfDirectorMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="GranteeStatusDomain" xlink:to="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:title="presentation: GranteeStatusDomain to ShareBasedPaymentArrangementBoardOfDirectorMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedPaymentArrangementEmployeeMember" xlink:label="ShareBasedPaymentArrangementEmployeeMember" xlink:title="ShareBasedPaymentArrangementEmployeeMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="GranteeStatusDomain" xlink:to="ShareBasedPaymentArrangementEmployeeMember" xlink:title="presentation: GranteeStatusDomain to ShareBasedPaymentArrangementEmployeeMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ExecutiveOfficerMember" xlink:label="ExecutiveOfficerMember" xlink:title="ExecutiveOfficerMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="GranteeStatusDomain" xlink:to="ExecutiveOfficerMember" xlink:title="presentation: GranteeStatusDomain to ExecutiveOfficerMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="GranteeStatusAxis" xlink:to="GranteeStatusDomain" xlink:title="presentation: GranteeStatusAxis to GranteeStatusDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="GranteeStatusAxis" xlink:title="presentation: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to GranteeStatusAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingAxis" xlink:label="VestingAxis" xlink:title="VestingAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VestingDomain" xlink:label="VestingDomain" xlink:title="VestingDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheOneMember" xlink:label="ShareBasedCompensationAwardTrancheOneMember" xlink:title="ShareBasedCompensationAwardTrancheOneMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="VestingDomain" xlink:to="ShareBasedCompensationAwardTrancheOneMember" xlink:title="presentation: VestingDomain to ShareBasedCompensationAwardTrancheOneMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheTwoMember" xlink:label="ShareBasedCompensationAwardTrancheTwoMember" xlink:title="ShareBasedCompensationAwardTrancheTwoMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="VestingDomain" xlink:to="ShareBasedCompensationAwardTrancheTwoMember" xlink:title="presentation: VestingDomain to ShareBasedCompensationAwardTrancheTwoMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAwardTrancheThreeMember" xlink:label="ShareBasedCompensationAwardTrancheThreeMember" xlink:title="ShareBasedCompensationAwardTrancheThreeMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="VestingDomain" xlink:to="ShareBasedCompensationAwardTrancheThreeMember" xlink:title="presentation: VestingDomain to ShareBasedCompensationAwardTrancheThreeMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="VestingAxis" xlink:to="VestingDomain" xlink:title="presentation: VestingAxis to VestingDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="VestingAxis" xlink:title="presentation: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to VestingAxis" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember" xlink:label="MinimumMember" xlink:title="MinimumMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RangeMember" xlink:to="MinimumMember" xlink:title="presentation: RangeMember to MinimumMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="MaximumMember" xlink:title="MaximumMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RangeMember" xlink:to="MaximumMember" xlink:title="presentation: RangeMember to MaximumMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RangeAxis" xlink:to="RangeMember" xlink:title="presentation: RangeAxis to RangeMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="RangeAxis" xlink:title="presentation: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to RangeAxis" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract to SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract to SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract to SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract to ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:to="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:title="presentation: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract to EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:to="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="presentation: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract to EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:to="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="presentation: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract to EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" xlink:title="presentation: ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems to EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:title="presentation: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:title="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="IncomeStatementLocationAxis" xlink:title="IncomeStatementLocationAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="IncomeStatementLocationDomain" xlink:title="IncomeStatementLocationDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfSalesMember" xlink:label="CostOfSalesMember" xlink:title="CostOfSalesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncomeStatementLocationDomain" xlink:to="CostOfSalesMember" xlink:title="presentation: IncomeStatementLocationDomain to CostOfSalesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchDevelopmentAndPatentExpensesMember" xlink:label="ResearchDevelopmentAndPatentExpensesMember" xlink:title="ResearchDevelopmentAndPatentExpensesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncomeStatementLocationDomain" xlink:to="ResearchDevelopmentAndPatentExpensesMember" xlink:title="presentation: IncomeStatementLocationDomain to ResearchDevelopmentAndPatentExpensesMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="SellingGeneralAndAdministrativeExpensesMember" xlink:title="SellingGeneralAndAdministrativeExpensesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncomeStatementLocationDomain" xlink:to="SellingGeneralAndAdministrativeExpensesMember" xlink:title="presentation: IncomeStatementLocationDomain to SellingGeneralAndAdministrativeExpensesMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncomeStatementLocationAxis" xlink:to="IncomeStatementLocationDomain" xlink:title="presentation: IncomeStatementLocationAxis to IncomeStatementLocationDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="IncomeStatementLocationAxis" xlink:title="presentation: ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable to IncomeStatementLocationAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationAbstract" xlink:label="ShareBasedCompensationAbstract" xlink:title="ShareBasedCompensationAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="AllocatedShareBasedCompensationExpense" xlink:title="AllocatedShareBasedCompensationExpense" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ShareBasedCompensationAbstract" xlink:to="AllocatedShareBasedCompensationExpense" xlink:title="presentation: ShareBasedCompensationAbstract to AllocatedShareBasedCompensationExpense" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="ShareBasedCompensationAbstract" xlink:title="presentation: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to ShareBasedCompensationAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="presentation: ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable to EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AccountingPoliciesAbstract" xlink:to="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:title="presentation: AccountingPoliciesAbstract to ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="presentation: AvailableForSaleSecuritiesDebtMaturitiesAbstract to AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="presentation: AvailableForSaleSecuritiesDebtMaturitiesAbstract to AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="presentation: AvailableForSaleSecuritiesDebtMaturitiesAbstract to AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="presentation: AvailableForSaleSecuritiesDebtMaturitiesAbstract to AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:title="presentation: AvailableForSaleSecuritiesDebtMaturitiesAbstract to AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_MaximumContractMaturityPeriodRange1" xlink:label="MaximumContractMaturityPeriodRange1" xlink:title="MaximumContractMaturityPeriodRange1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="MaximumContractMaturityPeriodRange1" xlink:title="presentation: AvailableForSaleSecuritiesDebtMaturitiesAbstract to MaximumContractMaturityPeriodRange1" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_MaximumContractMaturityPeriodRange2" xlink:label="MaximumContractMaturityPeriodRange2" xlink:title="MaximumContractMaturityPeriodRange2" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="MaximumContractMaturityPeriodRange2" xlink:title="presentation: AvailableForSaleSecuritiesDebtMaturitiesAbstract to MaximumContractMaturityPeriodRange2" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_MaximumContractMaturityPeriodRange3" xlink:label="MaximumContractMaturityPeriodRange3" xlink:title="MaximumContractMaturityPeriodRange3" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:to="MaximumContractMaturityPeriodRange3" xlink:title="presentation: AvailableForSaleSecuritiesDebtMaturitiesAbstract to MaximumContractMaturityPeriodRange3" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAbstract" xlink:to="AvailableForSaleSecuritiesDebtMaturitiesAbstract" xlink:title="presentation: InvestmentsAbstract to AvailableForSaleSecuritiesDebtMaturitiesAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsAllOtherInvestmentsAbstract" xlink:label="InvestmentsAllOtherInvestmentsAbstract" xlink:title="InvestmentsAllOtherInvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAllOtherInvestmentsAbstract" xlink:to="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="presentation: InvestmentsAllOtherInvestmentsAbstract to NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:label="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAllOtherInvestmentsAbstract" xlink:to="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" xlink:title="presentation: InvestmentsAllOtherInvestmentsAbstract to NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAbstract" xlink:to="InvestmentsAllOtherInvestmentsAbstract" xlink:title="presentation: InvestmentsAbstract to InvestmentsAllOtherInvestmentsAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="CorporateDebtSecuritiesMember" xlink:title="presentation: DebtSecuritiesMember to CorporateDebtSecuritiesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember" xlink:label="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="USGovernmentAgenciesDebtSecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="presentation: DebtSecuritiesMember to USGovernmentAgenciesDebtSecuritiesMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember" xlink:label="USTreasurySecuritiesMember" xlink:title="USTreasurySecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="USTreasurySecuritiesMember" xlink:title="presentation: DebtSecuritiesMember to USTreasurySecuritiesMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USStatesAndPoliticalSubdivisionsMember" xlink:label="USStatesAndPoliticalSubdivisionsMember" xlink:title="USStatesAndPoliticalSubdivisionsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="USStatesAndPoliticalSubdivisionsMember" xlink:title="presentation: DebtSecuritiesMember to USStatesAndPoliticalSubdivisionsMember" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherDebtSecuritiesMember" xlink:label="OtherDebtSecuritiesMember" xlink:title="OtherDebtSecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="OtherDebtSecuritiesMember" xlink:title="presentation: DebtSecuritiesMember to OtherDebtSecuritiesMember" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="DebtSecuritiesMember" xlink:title="presentation: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to DebtSecuritiesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesMember" xlink:label="EquitySecuritiesMember" xlink:title="EquitySecuritiesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_EquitySecuritiesPubliclyTradedCompaniesMember" xlink:label="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:title="EquitySecuritiesPubliclyTradedCompaniesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EquitySecuritiesMember" xlink:to="EquitySecuritiesPubliclyTradedCompaniesMember" xlink:title="presentation: EquitySecuritiesMember to EquitySecuritiesPubliclyTradedCompaniesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_EquitySecuritiesPrivateCompaniesMember" xlink:label="EquitySecuritiesPrivateCompaniesMember" xlink:title="EquitySecuritiesPrivateCompaniesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EquitySecuritiesMember" xlink:to="EquitySecuritiesPrivateCompaniesMember" xlink:title="presentation: EquitySecuritiesMember to EquitySecuritiesPrivateCompaniesMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="EquitySecuritiesMember" xlink:title="presentation: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to EquitySecuritiesMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="presentation: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentHoldingsTable" xlink:to="FinancialInstrumentAxis" xlink:title="presentation: InvestmentHoldingsTable to FinancialInstrumentAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentSecondaryCategorizationAxis" xlink:label="InvestmentSecondaryCategorizationAxis" xlink:title="InvestmentSecondaryCategorizationAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsBySecondaryCategorizationDomain" xlink:label="InvestmentsBySecondaryCategorizationDomain" xlink:title="InvestmentsBySecondaryCategorizationDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SecuritiesWithMaturityOfOneYearOrLessMember" xlink:label="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:title="SecuritiesWithMaturityOfOneYearOrLessMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsBySecondaryCategorizationDomain" xlink:to="SecuritiesWithMaturityOfOneYearOrLessMember" xlink:title="presentation: InvestmentsBySecondaryCategorizationDomain to SecuritiesWithMaturityOfOneYearOrLessMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:label="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:title="SecuritiesWithMaturityOfMoreThanOneYearMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsBySecondaryCategorizationDomain" xlink:to="SecuritiesWithMaturityOfMoreThanOneYearMember" xlink:title="presentation: InvestmentsBySecondaryCategorizationDomain to SecuritiesWithMaturityOfMoreThanOneYearMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentSecondaryCategorizationAxis" xlink:to="InvestmentsBySecondaryCategorizationDomain" xlink:title="presentation: InvestmentSecondaryCategorizationAxis to InvestmentsBySecondaryCategorizationDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentHoldingsTable" xlink:to="InvestmentSecondaryCategorizationAxis" xlink:title="presentation: InvestmentHoldingsTable to InvestmentSecondaryCategorizationAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:label="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:title="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_EquityMethodInvesteeNameDomain" xlink:label="EquityMethodInvesteeNameDomain" xlink:title="EquityMethodInvesteeNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BicycleTherapeuticsPlcMember" xlink:label="BicycleTherapeuticsPlcMember" xlink:title="BicycleTherapeuticsPlcMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EquityMethodInvesteeNameDomain" xlink:to="BicycleTherapeuticsPlcMember" xlink:title="presentation: EquityMethodInvesteeNameDomain to BicycleTherapeuticsPlcMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ProqrTherapeuticsNVMember" xlink:label="ProqrTherapeuticsNVMember" xlink:title="ProqrTherapeuticsNVMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EquityMethodInvesteeNameDomain" xlink:to="ProqrTherapeuticsNVMember" xlink:title="presentation: EquityMethodInvesteeNameDomain to ProqrTherapeuticsNVMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:to="EquityMethodInvesteeNameDomain" xlink:title="presentation: ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis to EquityMethodInvesteeNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentHoldingsTable" xlink:to="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:title="presentation: InvestmentHoldingsTable to ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:label="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:title="AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to AvailableForSaleDebtSecuritiesAmortizedCostBasis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" order="2.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="AvailableForSaleSecuritiesDebtSecurities" xlink:title="AvailableForSaleSecuritiesDebtSecurities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="AvailableForSaleSecuritiesDebtSecurities" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to AvailableForSaleSecuritiesDebtSecurities" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiCost" xlink:label="EquitySecuritiesFvNiCost" xlink:title="EquitySecuritiesFvNiCost" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="EquitySecuritiesFvNiCost" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to EquitySecuritiesFvNiCost" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiUnrealizedGain" xlink:label="EquitySecuritiesFvNiUnrealizedGain" xlink:title="EquitySecuritiesFvNiUnrealizedGain" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="EquitySecuritiesFvNiUnrealizedGain" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to EquitySecuritiesFvNiUnrealizedGain" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNiUnrealizedLoss" xlink:label="EquitySecuritiesFvNiUnrealizedLoss" xlink:title="EquitySecuritiesFvNiUnrealizedLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="EquitySecuritiesFvNiUnrealizedLoss" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to EquitySecuritiesFvNiUnrealizedLoss" order="6.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNi" xlink:label="EquitySecuritiesFvNi" xlink:title="EquitySecuritiesFvNi" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="EquitySecuritiesFvNi" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to EquitySecuritiesFvNi" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" order="9.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" order="10.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:label="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:title="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" order="11.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:label="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:title="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" xlink:title="presentation: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets" order="12.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="presentation: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentHoldingsTable" xlink:to="InvestmentHoldingsLineItems" xlink:title="presentation: InvestmentHoldingsTable to InvestmentHoldingsLineItems" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAbstract" xlink:to="InvestmentHoldingsTable" xlink:title="presentation: InvestmentsAbstract to InvestmentHoldingsTable" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="CorporateDebtSecuritiesMember" xlink:title="presentation: DebtSecuritiesMember to CorporateDebtSecuritiesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember" xlink:label="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="USGovernmentAgenciesDebtSecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="presentation: DebtSecuritiesMember to USGovernmentAgenciesDebtSecuritiesMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember" xlink:label="USTreasurySecuritiesMember" xlink:title="USTreasurySecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="USTreasurySecuritiesMember" xlink:title="presentation: DebtSecuritiesMember to USTreasurySecuritiesMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USStatesAndPoliticalSubdivisionsMember" xlink:label="USStatesAndPoliticalSubdivisionsMember" xlink:title="USStatesAndPoliticalSubdivisionsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="USStatesAndPoliticalSubdivisionsMember" xlink:title="presentation: DebtSecuritiesMember to USStatesAndPoliticalSubdivisionsMember" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherDebtSecuritiesMember" xlink:label="OtherDebtSecuritiesMember" xlink:title="OtherDebtSecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtSecuritiesMember" xlink:to="OtherDebtSecuritiesMember" xlink:title="presentation: DebtSecuritiesMember to OtherDebtSecuritiesMember" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="DebtSecuritiesMember" xlink:title="presentation: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to DebtSecuritiesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="presentation: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentHoldingsTable" xlink:to="FinancialInstrumentAxis" xlink:title="presentation: InvestmentHoldingsTable to FinancialInstrumentAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAbstract" xlink:label="AvailableForSaleSecuritiesAbstract" xlink:title="AvailableForSaleSecuritiesAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:title="presentation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:title="presentation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:label="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:title="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:to="DebtSecuritiesAvailableForSaleUnrealizedLossPosition" xlink:title="presentation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract to DebtSecuritiesAvailableForSaleUnrealizedLossPosition" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" xlink:title="presentation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" order="0.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:to="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="presentation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract to DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" order="1.0" preferredLabel="http://www.xbrl.org/2009/role/negatedLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:to="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:title="presentation: AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract to DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" order="2.0" preferredLabel="http://www.xbrl.org/2009/role/negatedTotalLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="AvailableForSaleSecuritiesAbstract" xlink:to="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:title="presentation: AvailableForSaleSecuritiesAbstract to AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentHoldingsLineItems" xlink:to="AvailableForSaleSecuritiesAbstract" xlink:title="presentation: InvestmentHoldingsLineItems to AvailableForSaleSecuritiesAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentHoldingsTable" xlink:to="InvestmentHoldingsLineItems" xlink:title="presentation: InvestmentHoldingsTable to InvestmentHoldingsLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="InvestmentsAbstract" xlink:to="InvestmentHoldingsTable" xlink:title="presentation: InvestmentsAbstract to InvestmentHoldingsTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/FairValueMeasurementsDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueDisclosuresAbstract" xlink:label="FairValueDisclosuresAbstract" xlink:title="FairValueDisclosuresAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="FairValueByMeasurementFrequencyAxis" xlink:title="FairValueByMeasurementFrequencyAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="FairValueMeasurementFrequencyDomain" xlink:title="FairValueMeasurementFrequencyDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsRecurringMember" xlink:label="FairValueMeasurementsRecurringMember" xlink:title="FairValueMeasurementsRecurringMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueMeasurementFrequencyDomain" xlink:to="FairValueMeasurementsRecurringMember" xlink:title="presentation: FairValueMeasurementFrequencyDomain to FairValueMeasurementsRecurringMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueByMeasurementFrequencyAxis" xlink:to="FairValueMeasurementFrequencyDomain" xlink:title="presentation: FairValueByMeasurementFrequencyAxis to FairValueMeasurementFrequencyDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="FairValueByMeasurementFrequencyAxis" xlink:title="presentation: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to FairValueByMeasurementFrequencyAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="FairValueByFairValueHierarchyLevelAxis" xlink:title="FairValueByFairValueHierarchyLevelAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="FairValueMeasurementsFairValueHierarchyDomain" xlink:title="FairValueMeasurementsFairValueHierarchyDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel1Member" xlink:label="FairValueInputsLevel1Member" xlink:title="FairValueInputsLevel1Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueMeasurementsFairValueHierarchyDomain" xlink:to="FairValueInputsLevel1Member" xlink:title="presentation: FairValueMeasurementsFairValueHierarchyDomain to FairValueInputsLevel1Member" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel2Member" xlink:label="FairValueInputsLevel2Member" xlink:title="FairValueInputsLevel2Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueMeasurementsFairValueHierarchyDomain" xlink:to="FairValueInputsLevel2Member" xlink:title="presentation: FairValueMeasurementsFairValueHierarchyDomain to FairValueInputsLevel2Member" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="FairValueInputsLevel3Member" xlink:title="FairValueInputsLevel3Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueMeasurementsFairValueHierarchyDomain" xlink:to="FairValueInputsLevel3Member" xlink:title="presentation: FairValueMeasurementsFairValueHierarchyDomain to FairValueInputsLevel3Member" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueByFairValueHierarchyLevelAxis" xlink:to="FairValueMeasurementsFairValueHierarchyDomain" xlink:title="presentation: FairValueByFairValueHierarchyLevelAxis to FairValueMeasurementsFairValueHierarchyDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="FairValueByFairValueHierarchyLevelAxis" xlink:title="presentation: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to FairValueByFairValueHierarchyLevelAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:label="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="CorporateDebtSecuritiesMember" xlink:title="presentation: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to CorporateDebtSecuritiesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember" xlink:label="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="USGovernmentAgenciesDebtSecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="USGovernmentAgenciesDebtSecuritiesMember" xlink:title="presentation: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to USGovernmentAgenciesDebtSecuritiesMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember" xlink:label="USTreasurySecuritiesMember" xlink:title="USTreasurySecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="USTreasurySecuritiesMember" xlink:title="presentation: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to USTreasurySecuritiesMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USStatesAndPoliticalSubdivisionsMember" xlink:label="USStatesAndPoliticalSubdivisionsMember" xlink:title="USStatesAndPoliticalSubdivisionsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="USStatesAndPoliticalSubdivisionsMember" xlink:title="presentation: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to USStatesAndPoliticalSubdivisionsMember" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherDebtSecuritiesMember" xlink:label="OtherDebtSecuritiesMember" xlink:title="OtherDebtSecuritiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:to="OtherDebtSecuritiesMember" xlink:title="presentation: TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain to OtherDebtSecuritiesMember" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FinancialInstrumentAxis" xlink:to="TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" xlink:title="presentation: FinancialInstrumentAxis to TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="FinancialInstrumentAxis" xlink:title="presentation: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to FinancialInstrumentAxis" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:label="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:title="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_EquityMethodInvesteeNameDomain" xlink:label="EquityMethodInvesteeNameDomain" xlink:title="EquityMethodInvesteeNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BicycleTherapeuticsPlcMember" xlink:label="BicycleTherapeuticsPlcMember" xlink:title="BicycleTherapeuticsPlcMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EquityMethodInvesteeNameDomain" xlink:to="BicycleTherapeuticsPlcMember" xlink:title="presentation: EquityMethodInvesteeNameDomain to BicycleTherapeuticsPlcMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ProqrTherapeuticsNVMember" xlink:label="ProqrTherapeuticsNVMember" xlink:title="ProqrTherapeuticsNVMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="EquityMethodInvesteeNameDomain" xlink:to="ProqrTherapeuticsNVMember" xlink:title="presentation: EquityMethodInvesteeNameDomain to ProqrTherapeuticsNVMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:to="EquityMethodInvesteeNameDomain" xlink:title="presentation: ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis to EquityMethodInvesteeNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" xlink:title="presentation: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="BalanceSheetLocationAxis" xlink:title="BalanceSheetLocationAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="BalanceSheetLocationDomain" xlink:title="BalanceSheetLocationDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsMember" xlink:label="CashAndCashEquivalentsMember" xlink:title="CashAndCashEquivalentsMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="BalanceSheetLocationDomain" xlink:to="CashAndCashEquivalentsMember" xlink:title="presentation: BalanceSheetLocationDomain to CashAndCashEquivalentsMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="BalanceSheetLocationAxis" xlink:to="BalanceSheetLocationDomain" xlink:title="presentation: BalanceSheetLocationAxis to BalanceSheetLocationDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="BalanceSheetLocationAxis" xlink:title="presentation: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to BalanceSheetLocationAxis" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="presentation: DebtInstrumentAxis to DebtInstrumentNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="DebtInstrumentAxis" xlink:title="presentation: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to DebtInstrumentAxis" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:title="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueNetAssetLiabilityAbstract" xlink:label="FairValueNetAssetLiabilityAbstract" xlink:title="FairValueNetAssetLiabilityAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="CashAndCashEquivalentsFairValueDisclosure" xlink:title="CashAndCashEquivalentsFairValueDisclosure" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="CashAndCashEquivalentsFairValueDisclosure" xlink:title="presentation: FairValueNetAssetLiabilityAbstract to CashAndCashEquivalentsFairValueDisclosure" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="AvailableForSaleSecuritiesDebtSecurities" xlink:title="AvailableForSaleSecuritiesDebtSecurities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="AvailableForSaleSecuritiesDebtSecurities" xlink:title="presentation: FairValueNetAssetLiabilityAbstract to AvailableForSaleSecuritiesDebtSecurities" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquitySecuritiesFvNi" xlink:label="EquitySecuritiesFvNi" xlink:title="EquitySecuritiesFvNi" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="EquitySecuritiesFvNi" xlink:title="presentation: FairValueNetAssetLiabilityAbstract to EquitySecuritiesFvNi" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="AssetsFairValueDisclosure" xlink:title="AssetsFairValueDisclosure" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="AssetsFairValueDisclosure" xlink:title="presentation: FairValueNetAssetLiabilityAbstract to AssetsFairValueDisclosure" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/totalLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="presentation: FairValueNetAssetLiabilityAbstract to DebtInstrumentInterestRateStatedPercentage" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NotesPayableFairValueDisclosure" xlink:label="NotesPayableFairValueDisclosure" xlink:title="NotesPayableFairValueDisclosure" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueNetAssetLiabilityAbstract" xlink:to="NotesPayableFairValueDisclosure" xlink:title="presentation: FairValueNetAssetLiabilityAbstract to NotesPayableFairValueDisclosure" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="FairValueNetAssetLiabilityAbstract" xlink:title="presentation: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems to FairValueNetAssetLiabilityAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:title="presentation: FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable to FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="FairValueDisclosuresAbstract" xlink:to="FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:title="presentation: FairValueDisclosuresAbstract to FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/IncomeTaxesDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxDisclosureAbstract" xlink:label="IncomeTaxDisclosureAbstract" xlink:title="IncomeTaxDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_AmortizationPeriodForResearchAndDevelopmentExpenditures" xlink:label="AmortizationPeriodForResearchAndDevelopmentExpenditures" xlink:title="AmortizationPeriodForResearchAndDevelopmentExpenditures" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncomeTaxDisclosureAbstract" xlink:to="AmortizationPeriodForResearchAndDevelopmentExpenditures" xlink:title="presentation: IncomeTaxDisclosureAbstract to AmortizationPeriodForResearchAndDevelopmentExpenditures" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="IncomeTaxExpenseBenefit" xlink:title="IncomeTaxExpenseBenefit" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="IncomeTaxDisclosureAbstract" xlink:to="IncomeTaxExpenseBenefit" xlink:title="presentation: IncomeTaxDisclosureAbstract to IncomeTaxExpenseBenefit" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails">
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis" xlink:label="TypeOfArrangementAxis" xlink:title="TypeOfArrangementAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember" xlink:label="ArrangementsAndNonarrangementTransactionsMember" xlink:title="ArrangementsAndNonarrangementTransactionsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaborationsMember" xlink:label="BiogenCollaborationsMember" xlink:title="BiogenCollaborationsMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:label="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="BiogenCollaboration2013StrategicNeurologyMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="BiogenCollaborationsMember" xlink:to="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="presentation: BiogenCollaborationsMember to BiogenCollaboration2013StrategicNeurologyMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ArrangementsAndNonarrangementTransactionsMember" xlink:to="BiogenCollaborationsMember" xlink:title="presentation: ArrangementsAndNonarrangementTransactionsMember to BiogenCollaborationsMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="TypeOfArrangementAxis" xlink:to="ArrangementsAndNonarrangementTransactionsMember" xlink:title="presentation: TypeOfArrangementAxis to ArrangementsAndNonarrangementTransactionsMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="TypeOfArrangementAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to TypeOfArrangementAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember" xlink:label="MaximumMember" xlink:title="MaximumMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RangeMember" xlink:to="MaximumMember" xlink:title="presentation: RangeMember to MaximumMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="RangeAxis" xlink:to="RangeMember" xlink:title="presentation: RangeAxis to RangeMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="RangeAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to RangeAxis" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_SpinrazaRoyaltiesMember" xlink:label="SpinrazaRoyaltiesMember" xlink:title="SpinrazaRoyaltiesMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="SpinrazaRoyaltiesMember" xlink:title="presentation: ProductsAndServicesDomain to SpinrazaRoyaltiesMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ResearchAndDevelopmentRevenueMember" xlink:label="ResearchAndDevelopmentRevenueMember" xlink:title="ResearchAndDevelopmentRevenueMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="ResearchAndDevelopmentRevenueMember" xlink:title="presentation: ProductsAndServicesDomain to ResearchAndDevelopmentRevenueMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_Ion541Member" xlink:label="Ion541Member" xlink:title="Ion541Member" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductsAndServicesDomain" xlink:to="Ion541Member" xlink:title="presentation: ProductsAndServicesDomain to Ion541Member" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ProductOrServiceAxis" xlink:to="ProductsAndServicesDomain" xlink:title="presentation: ProductOrServiceAxis to ProductsAndServicesDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ProductOrServiceAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ProductOrServiceAxis" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis" xlink:label="ConcentrationRiskByBenchmarkAxis" xlink:title="ConcentrationRiskByBenchmarkAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain" xlink:label="ConcentrationRiskBenchmarkDomain" xlink:title="ConcentrationRiskBenchmarkDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerMember" xlink:label="RevenueFromContractWithCustomerMember" xlink:title="RevenueFromContractWithCustomerMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConcentrationRiskBenchmarkDomain" xlink:to="RevenueFromContractWithCustomerMember" xlink:title="presentation: ConcentrationRiskBenchmarkDomain to RevenueFromContractWithCustomerMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConcentrationRiskByBenchmarkAxis" xlink:to="ConcentrationRiskBenchmarkDomain" xlink:title="presentation: ConcentrationRiskByBenchmarkAxis to ConcentrationRiskBenchmarkDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ConcentrationRiskByBenchmarkAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ConcentrationRiskByBenchmarkAxis" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis" xlink:label="ConcentrationRiskByTypeAxis" xlink:title="ConcentrationRiskByTypeAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain" xlink:label="ConcentrationRiskTypeDomain" xlink:title="ConcentrationRiskTypeDomain" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="CustomerConcentrationRiskMember" xlink:title="CustomerConcentrationRiskMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConcentrationRiskTypeDomain" xlink:to="CustomerConcentrationRiskMember" xlink:title="presentation: ConcentrationRiskTypeDomain to CustomerConcentrationRiskMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConcentrationRiskByTypeAxis" xlink:to="ConcentrationRiskTypeDomain" xlink:title="presentation: ConcentrationRiskByTypeAxis to ConcentrationRiskTypeDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="ConcentrationRiskByTypeAxis" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to ConcentrationRiskByTypeAxis" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CumulativePaymentsReceived" xlink:label="CumulativePaymentsReceived" xlink:title="CumulativePaymentsReceived" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="CumulativePaymentsReceived" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to CumulativePaymentsReceived" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to RevenueFromContractWithCustomerExcludingAssessedTax" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="ConcentrationRiskPercentage1" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to ConcentrationRiskPercentage1" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiability" xlink:label="ContractWithCustomerLiability" xlink:title="ContractWithCustomerLiability" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="ContractWithCustomerLiability" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to ContractWithCustomerLiability" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NumberOfTargetsAdvanced" xlink:label="NumberOfTargetsAdvanced" xlink:title="NumberOfTargetsAdvanced" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NumberOfTargetsAdvanced" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NumberOfTargetsAdvanced" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_NextPotentialPayment" xlink:label="NextPotentialPayment" xlink:title="NextPotentialPayment" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="NextPotentialPayment" xlink:title="presentation: CollaborativeArrangementAndLicensingAgreementAbstract to NextPotentialPayment" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="presentation: CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems to CollaborativeArrangementAndLicensingAgreementAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="presentation: ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable to CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:to="ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:title="presentation: CollaborativeArrangementsAndLicensingAgreementsAbstract to ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com/role/ConvertibleDebtDetails">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtDisclosureAbstract" xlink:label="DebtDisclosureAbstract" xlink:title="DebtDisclosureAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentTable" xlink:label="DebtInstrumentTable" xlink:title="DebtInstrumentTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentAxis" xlink:label="DebtInstrumentAxis" xlink:title="DebtInstrumentAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentNameDomain" xlink:label="DebtInstrumentNameDomain" xlink:title="DebtInstrumentNameDomain" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0PercentMember" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes0125PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes0125PercentMember" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentNameDomain" xlink:to="ConvertibleSeniorNotes1PercentMember" xlink:title="presentation: DebtInstrumentNameDomain to ConvertibleSeniorNotes1PercentMember" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentAxis" xlink:to="DebtInstrumentNameDomain" xlink:title="presentation: DebtInstrumentAxis to DebtInstrumentNameDomain" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentTable" xlink:to="DebtInstrumentAxis" xlink:title="presentation: DebtInstrumentTable to DebtInstrumentAxis" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentLineItems" xlink:label="DebtInstrumentLineItems" xlink:title="DebtInstrumentLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:label="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:title="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="DebtInstrumentFaceAmount" xlink:title="DebtInstrumentFaceAmount" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentFaceAmount" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentFaceAmount" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/verboseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentRepurchasedFaceAmount" xlink:label="DebtInstrumentRepurchasedFaceAmount" xlink:title="DebtInstrumentRepurchasedFaceAmount" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentRepurchasedFaceAmount" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentRepurchasedFaceAmount" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfConvertibleDebt" xlink:label="RepaymentsOfConvertibleDebt" xlink:title="RepaymentsOfConvertibleDebt" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="RepaymentsOfConvertibleDebt" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to RepaymentsOfConvertibleDebt" order="2.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="DebtInstrumentCarryingAmount" xlink:title="DebtInstrumentCarryingAmount" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentCarryingAmount" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentCarryingAmount" order="3.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredFinanceCostsNet" xlink:label="DeferredFinanceCostsNet" xlink:title="DeferredFinanceCostsNet" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DeferredFinanceCostsNet" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DeferredFinanceCostsNet" order="4.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentMaturityDate" xlink:label="DebtInstrumentMaturityDate" xlink:title="DebtInstrumentMaturityDate" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentMaturityDate" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentMaturityDate" order="5.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage" xlink:label="DebtInstrumentInterestRateStatedPercentage" xlink:title="DebtInstrumentInterestRateStatedPercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentInterestRateStatedPercentage" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentInterestRateStatedPercentage" order="6.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="DebtInstrumentInterestRateEffectivePercentage" xlink:title="DebtInstrumentInterestRateEffectivePercentage" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentInterestRateEffectivePercentage" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentInterestRateEffectivePercentage" order="7.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:label="DebtInstrumentConvertibleConversionPrice1" xlink:title="DebtInstrumentConvertibleConversionPrice1" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentConvertibleConversionPrice1" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentConvertibleConversionPrice1" order="8.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:label="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentConvertibleConversionPriceIncludingCallSpread" order="9.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:label="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="DebtInstrumentConvertibleSharesSubjectToConversion" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentConvertibleSharesSubjectToConversion" order="10.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_CallSpread" xlink:label="CallSpread" xlink:title="CallSpread" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="CallSpread" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to CallSpread" order="11.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsForHedgeFinancingActivities" xlink:label="PaymentsForHedgeFinancingActivities" xlink:title="PaymentsForHedgeFinancingActivities" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="PaymentsForHedgeFinancingActivities" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to PaymentsForHedgeFinancingActivities" order="12.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfWarrants" xlink:label="ProceedsFromIssuanceOfWarrants" xlink:title="ProceedsFromIssuanceOfWarrants" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="ProceedsFromIssuanceOfWarrants" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to ProceedsFromIssuanceOfWarrants" order="13.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt" xlink:label="GainsLossesOnExtinguishmentOfDebt" xlink:title="GainsLossesOnExtinguishmentOfDebt" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="GainsLossesOnExtinguishmentOfDebt" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to GainsLossesOnExtinguishmentOfDebt" order="14.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:type="locator" xlink:href="ions-20220331.xsd#ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:label="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="presentation: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" order="15.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentLineItems" xlink:to="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:title="presentation: DebtInstrumentLineItems to ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtInstrumentTable" xlink:to="DebtInstrumentLineItems" xlink:title="presentation: DebtInstrumentTable to DebtInstrumentLineItems" order="1.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="DebtDisclosureAbstract" xlink:to="DebtInstrumentTable" xlink:title="presentation: DebtDisclosureAbstract to DebtInstrumentTable" order="0.0" preferredLabel="http://www.xbrl.org/2003/role/label" />
  </link:presentationLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>11
<FILENAME>R1.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624038639384">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Document and Entity Information - shares<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2022</div></th>
<th class="th"><div>Apr. 28, 2022</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_dei_CoverAbstract', window );"><strong>Cover [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_dei_DocumentType', window );">Document Type</a></td>
<td class="text">10-Q<span></span>
</td>
<td class="text">&#160;<span></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_dei_AmendmentFlag', window );">Amendment Flag</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></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_dei_DocumentQuarterlyReport', window );">Document Quarterly Report</a></td>
<td class="text">true<span></span>
</td>
<td class="text">&#160;<span></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_dei_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Mar. 31,  2022<span></span>
</td>
<td class="text">&#160;<span></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_dei_CurrentFiscalYearEndDate', window );">Current Fiscal Year End Date</a></td>
<td class="text">--12-31<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_dei_DocumentFiscalYearFocus', window );">Document Fiscal Year Focus</a></td>
<td class="text">2022<span></span>
</td>
<td class="text">&#160;<span></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_dei_DocumentFiscalPeriodFocus', window );">Document Fiscal Period Focus</a></td>
<td class="text">Q1<span></span>
</td>
<td class="text">&#160;<span></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_dei_DocumentTransitionReport', window );">Document Transition Report</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></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_dei_EntityFileNumber', window );">Entity File Number</a></td>
<td class="text">000-19125<span></span>
</td>
<td class="text">&#160;<span></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_dei_EntityRegistrantName', window );">Entity Registrant Name</a></td>
<td class="text">Ionis Pharmaceuticals, Inc.<span></span>
</td>
<td class="text">&#160;<span></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_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<span></span>
</td>
<td class="text">&#160;<span></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_dei_EntityIncorporationStateCountryCode', window );">Entity Incorporation, State or Country Code</a></td>
<td class="text">DE<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_dei_EntityTaxIdentificationNumber', window );">Entity Tax Identification Number</a></td>
<td class="text">33-0336973<span></span>
</td>
<td class="text">&#160;<span></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_dei_EntityAddressAddressLine1', window );">Entity Address, Address Line One</a></td>
<td class="text">2855 Gazelle Court<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_dei_EntityAddressCityOrTown', window );">Entity Address, City or Town</a></td>
<td class="text">Carlsbad<span></span>
</td>
<td class="text">&#160;<span></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_dei_EntityAddressStateOrProvince', window );">Entity Address, State or Province</a></td>
<td class="text">CA<span></span>
</td>
<td class="text">&#160;<span></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_dei_EntityAddressPostalZipCode', window );">Entity Address, Postal Zip Code</a></td>
<td class="text">92010<span></span>
</td>
<td class="text">&#160;<span></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_dei_CityAreaCode', window );">City Area Code</a></td>
<td class="text">760<span></span>
</td>
<td class="text">&#160;<span></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_dei_LocalPhoneNumber', window );">Local Phone Number</a></td>
<td class="text">931-9200<span></span>
</td>
<td class="text">&#160;<span></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_dei_Security12bTitle', window );">Title of 12(b) Security</a></td>
<td class="text">Common Stock, $.001 Par Value<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_dei_TradingSymbol', window );">Trading Symbol</a></td>
<td class="text">IONS<span></span>
</td>
<td class="text">&#160;<span></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_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 custom" 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 custom" 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 custom" 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 custom" 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 custom" 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 custom" 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 custom" 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">141,797,854<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 YYYY format. For a 2006 annual report, which may also provide financial information from prior periods, fiscal 2006 should be given as the fiscal year focus. Example: 2006.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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>For the EDGAR submission types of Form 8-K: the date of the report, the date of the earliest event reported; for the EDGAR submission types of Form N-1A: the filing date; for all other submission types: the end of the reporting or transition period.  The format of the date is YYYY-MM-DD.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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 308<br> -Subsection a<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ 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 Exchange Act<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 Exchange Act<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 Exchange Act<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 Exchange Act<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 Exchange Act<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 Exchange Act<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 Exchange Act<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>12
<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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624040714248">
<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, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" 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">$ 542,513<span></span>
</td>
<td class="nump">$ 869,191<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Short-term investments</a></td>
<td class="nump">1,509,880<span></span>
</td>
<td class="nump">1,245,782<span></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_us-gaap_ContractWithCustomerAssetNetCurrent', window );">Contracts receivable</a></td>
<td class="nump">26,122<span></span>
</td>
<td class="nump">61,896<span></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_us-gaap_InventoryNet', window );">Inventories</a></td>
<td class="nump">24,032<span></span>
</td>
<td class="nump">24,806<span></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_us-gaap_OtherAssetsCurrent', window );">Other current assets</a></td>
<td class="nump">150,577<span></span>
</td>
<td class="nump">143,374<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_us-gaap_AssetsCurrent', window );">Total current assets</a></td>
<td class="nump">2,253,124<span></span>
</td>
<td class="nump">2,345,049<span></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_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">177,724<span></span>
</td>
<td class="nump">178,069<span></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_us-gaap_FiniteLivedIntangibleAssetsNet', window );">Patents, net</a></td>
<td class="nump">29,295<span></span>
</td>
<td class="nump">29,005<span></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_us-gaap_OtherAssetsNoncurrent', window );">Deposits and other assets</a></td>
<td class="nump">58,949<span></span>
</td>
<td class="nump">59,567<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_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">2,519,092<span></span>
</td>
<td class="nump">2,611,690<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" 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">16,125<span></span>
</td>
<td class="nump">11,904<span></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_us-gaap_EmployeeRelatedLiabilitiesCurrent', window );">Accrued compensation</a></td>
<td class="nump">16,525<span></span>
</td>
<td class="nump">38,810<span></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_us-gaap_AccruedLiabilitiesCurrent', window );">Accrued liabilities</a></td>
<td class="nump">99,256<span></span>
</td>
<td class="nump">88,560<span></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_us-gaap_AccruedIncomeTaxesCurrent', window );">Income taxes payable</a></td>
<td class="nump">901<span></span>
</td>
<td class="nump">36<span></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_LongTermObligationsExcludingConvertibleDebtCurrent', window );">Current portion of long-term obligations</a></td>
<td class="nump">4,206<span></span>
</td>
<td class="nump">3,526<span></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_us-gaap_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred contract revenue</a></td>
<td class="nump">91,437<span></span>
</td>
<td class="nump">97,714<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_us-gaap_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">228,450<span></span>
</td>
<td class="nump">240,550<span></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_us-gaap_ContractWithCustomerLiabilityNoncurrent', window );">Long-term deferred contract revenue</a></td>
<td class="nump">333,138<span></span>
</td>
<td class="nump">351,879<span></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_LongTermObligationsExcludingConvertibleDebtNoncurrent', window );">Long-term obligations, less current portion</a></td>
<td class="nump">25,710<span></span>
</td>
<td class="nump">26,378<span></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_us-gaap_LongTermLoansFromBank', window );">Long-term mortgage debt</a></td>
<td class="nump">59,462<span></span>
</td>
<td class="nump">59,713<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_us-gaap_Liabilities', window );">Total liabilities</a></td>
<td class="nump">1,809,518<span></span>
</td>
<td class="nump">1,839,953<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" 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, 141,753,122 and 141,210,015 shares issued and outstanding at March 31, 2022 (unaudited) and December 31, 2021, respectively</a></td>
<td class="nump">142<span></span>
</td>
<td class="nump">141<span></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_us-gaap_AdditionalPaidInCapitalCommonStock', window );">Additional paid-in capital</a></td>
<td class="nump">1,983,078<span></span>
</td>
<td class="nump">1,964,167<span></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_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax', window );">Accumulated other comprehensive loss</a></td>
<td class="num">(48,578)<span></span>
</td>
<td class="num">(32,668)<span></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_us-gaap_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="num">(1,225,068)<span></span>
</td>
<td class="num">(1,159,903)<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_us-gaap_StockholdersEquity', window );">Total stockholders' equity</a></td>
<td class="nump">709,574<span></span>
</td>
<td class="nump">771,737<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_us-gaap_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">2,519,092<span></span>
</td>
<td class="nump">2,611,690<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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 custom" 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">619,898<span></span>
</td>
<td class="nump">619,119<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" 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">$ 542,860<span></span>
</td>
<td class="nump">$ 542,314<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsExcludingConvertibleDebtCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 obligations, excluding convertible debt, classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligationsExcludingConvertibleDebtCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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_LongTermObligationsExcludingConvertibleDebtNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 obligations, excluding convertible debt, 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_LongTermObligationsExcludingConvertibleDebtNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<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><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccountsPayableCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedIncomeTaxesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Carrying amount as of the balance sheet date of the unpaid sum of the known and estimated amounts payable to satisfy all currently due domestic and foreign income tax obligations.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(15)(b)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15)(1))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedIncomeTaxesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred and payable, pertaining to costs that are statutory in nature, are incurred on contractual obligations, or accumulate over time and for which invoices have not yet been received or will not be rendered. Examples include taxes, interest, rent and utilities. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Accumulated change in equity from transactions and other events and circumstances from non-owner sources, net of tax effect, at period end. Excludes Net Income (Loss), and accumulated changes in equity from transactions resulting from investments by owners and distributions to owners. Includes foreign currency translation items, certain pension adjustments, unrealized gains and losses on certain investments in debt and equity securities, other than temporary impairment (OTTI) losses related to factors other than credit losses on available-for-sale and held-to-maturity debt securities that an entity does not intend to sell and it is not more likely than not that the entity will be required to sell before recovery of the amortized cost basis, as well as changes in the fair value of derivatives related to the effective portion of a designated cash flow hedge.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(4))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=124509347&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=124509347&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=124501264&amp;loc=SL117420844-207641<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(ii)<br> -URI http://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -URI http://asc.fasb.org/extlink&amp;oid=124509347&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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Assets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all assets that are recognized. Assets are probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(11))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<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 22<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8736-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 6: 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 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<br><br>Reference 9: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 12: 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 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 14: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 17: 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=123419778&amp;loc=d3e5710-111685<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 19: 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 20: http://www.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=123359005&amp;loc=d3e8933-108599<br><br>Reference 21: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 22: 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 23: http://www.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=123359005&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=124098289&amp;loc=d3e6801-107765<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<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 210.5-02.9)<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 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 9: 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=123596393&amp;loc=d3e14064-108612<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 12: 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 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 14: 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 15: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 17: 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=123419778&amp;loc=d3e5710-111685<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<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://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=124098289&amp;loc=d3e6676-107765<br><br>Reference 21: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AssetsCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=124260329&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=123570139&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=124098289&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://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI 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=123360276&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=123360276&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=123351226&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=123360276&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=123360276&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=123351226&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=123360276&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=123360276&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=123351226&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_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=124098289&amp;loc=d3e6676-107765<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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://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 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8906-108599<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<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 (b)<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 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 7: 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=123596393&amp;loc=d3e14064-108612<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 9: 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=123419778&amp;loc=d3e5710-111685<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 12: 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=123419778&amp;loc=d3e5710-111685<br><br>Reference 13: 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 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 20: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(32))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 7: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123596393&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/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<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 (b)<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 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 7: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 10: 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=123419778&amp;loc=d3e5710-111685<br><br>Reference 11: 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 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 14: 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=123419778&amp;loc=d3e5710-111685<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 19: 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=123596393&amp;loc=d3e14064-108612<br><br>Reference 20: 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></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 360<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=124429447&amp;loc=SL124453093-239630<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(13))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 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 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(4))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400017&amp;loc=d3e572229-122910<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=124501264&amp;loc=SL117420844-207641<br><br>Reference 6: 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 7: 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=124501264&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://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -URI http://asc.fasb.org/extlink&amp;oid=122038336&amp;loc=d3e74512-122707<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(31))<br> -URI 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(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 7: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI 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_StockholdersEquity</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance 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_StockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>13
<FILENAME>R3.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624040665560">
<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, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" 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 custom" 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 custom" 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">141,753,122<span></span>
</td>
<td class="nump">141,210,015<span></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_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="nump">141,753,122<span></span>
</td>
<td class="nump">141,210,015<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" 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">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockParOrStatedValuePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Face amount or stated value per share of common stock.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockParOrStatedValuePerShare</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The maximum number of common shares permitted to be issued by an entity's charter and bylaws.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total number of common shares of an entity that have been sold or granted to shareholders (includes common shares that were issued, repurchased and remain in the treasury). These shares represent capital invested by the firm's shareholders and owners, and may be all or only a portion of the number of shares authorized. Shares issued include shares outstanding and shares held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of shares of common stock outstanding. Common stock represent the ownership interest in a corporation.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=123467817&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI http://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI 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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesAndStockholdersEquityAbstract</td>
</tr>
<tr>
<td style="padding-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_StockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>14
<FILENAME>R4.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624039374776">
<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, 2022</div></th>
<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_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 custom" 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">$ 141,919<span></span>
</td>
<td class="nump">$ 111,607<span></span>
</td>
</tr>
<tr class="re">
<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 custom" 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">4,170<span></span>
</td>
<td class="nump">2,578<span></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">161,126<span></span>
</td>
<td class="nump">139,801<span></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_us-gaap_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="nump">34,127<span></span>
</td>
<td class="nump">61,199<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_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">199,423<span></span>
</td>
<td class="nump">203,578<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_us-gaap_OperatingIncomeLoss', window );">Loss from operations</a></td>
<td class="num">(57,504)<span></span>
</td>
<td class="num">(91,971)<span></span>
</td>
</tr>
<tr class="re">
<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 custom" 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">1,993<span></span>
</td>
<td class="nump">4,643<span></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_us-gaap_InterestExpense', window );">Interest expense</a></td>
<td class="num">(2,122)<span></span>
</td>
<td class="num">(2,414)<span></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_us-gaap_GainLossOnInvestments', window );">Loss on investments</a></td>
<td class="num">(6,625)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OtherNonoperatingIncomeExpense', window );">Other income</a></td>
<td class="nump">187<span></span>
</td>
<td class="nump">3<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_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest', window );">Loss before income tax expense</a></td>
<td class="num">(64,071)<span></span>
</td>
<td class="num">(89,739)<span></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_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax expense</a></td>
<td class="num">(1,094)<span></span>
</td>
<td class="num">(130)<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_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (65,165)<span></span>
</td>
<td class="num">$ (89,869)<span></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_us-gaap_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="num">$ (0.46)<span></span>
</td>
<td class="num">$ (0.64)<span></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_us-gaap_EarningsPerShareDiluted', window );">Diluted net loss per share (in dollars per share)</a></td>
<td class="num">$ (0.46)<span></span>
</td>
<td class="num">$ (0.64)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">141,599<span></span>
</td>
<td class="nump">140,770<span></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_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net loss per share (in shares)</a></td>
<td class="nump">141,599<span></span>
</td>
<td class="nump">140,770<span></span>
</td>
</tr>
<tr 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="ro">
<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 custom" 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">$ 72,285<span></span>
</td>
<td class="nump">$ 84,448<span></span>
</td>
</tr>
<tr 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="re">
<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 custom" 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">53,818<span></span>
</td>
<td class="nump">59,986<span></span>
</td>
</tr>
<tr 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="ro">
<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 custom" 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">6,160<span></span>
</td>
<td class="nump">19,838<span></span>
</td>
</tr>
<tr 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="re">
<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 custom" 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">12,307<span></span>
</td>
<td class="nump">4,624<span></span>
</td>
</tr>
<tr 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_ResearchAndDevelopmentRevenueMember', window );">Research and Development 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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">69,634<span></span>
</td>
<td class="nump">27,159<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_CollaborativeAgreementRevenueMember', window );">Collaborative Agreement 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 custom" 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">49,784<span></span>
</td>
<td class="nump">27,159<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_EplontersenJointDevelopmentRevenueMember', window );">Eplontersen Joint Development 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 custom" 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">$ 19,850<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ResearchDevelopmentAndPatentExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects. Also includes charges for amortization and write-downs of capitalized patent costs, as well as legal fees for patent litigation and patent defense.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ResearchDevelopmentAndPatentExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostOfGoodsAndServicesSold">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs related to goods produced and sold and services rendered by an entity during the reporting period. This excludes costs incurred during the reporting period related to financial services rendered and other revenue generating activities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.2(a),(d))<br> -URI http://asc.fasb.org/extlink&amp;oid=123367319&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostOfGoodsAndServicesSold</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total costs of sales and operating expenses for the period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI http://asc.fasb.org/extlink&amp;oid=123367319&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostsAndExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpensesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostsAndExpensesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=d3e1448-109256<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 4<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<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 11<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=d3e1337-109256<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 9: 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=125512782&amp;loc=d3e4984-109258<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<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 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=125512782&amp;loc=d3e3842-109258<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 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22644-107794<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 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<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=123367319&amp;loc=SL114868664-224227<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=d3e1252-109256<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=SL5780133-109256<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI 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>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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=125512782&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=124431687&amp;loc=d3e22644-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=125512782&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=125511455&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=124431687&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=d3e1337-109256<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -URI http://asc.fasb.org/extlink&amp;oid=123367319&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>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=123581744&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=123367319&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=123570139&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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="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 (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8933-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8906-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8933-108599<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 940<br> -SubTopic 20<br> -Section 25<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=123384075&amp;loc=d3e41242-110953<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8736-108599<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -URI http://asc.fasb.org/extlink&amp;oid=123367319&amp;loc=SL114868664-224227<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(8))<br> -URI 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 942<br> -SubTopic 235<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399901&amp;loc=d3e537907-122884<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8924-108599<br><br>Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -URI 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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&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=124431687&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123586238&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI 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=124431687&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=124435984&amp;loc=d3e28555-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&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=123367319&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=123367319&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=123367319&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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(18))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=124431353&amp;loc=SL124452729-227067<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 8: 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(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=123367319&amp;loc=SL114868664-224227<br><br>Reference 9: 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=123570139&amp;loc=d3e3602-108585<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 1<br> -Subparagraph (b)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22499-107794<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22663-107794<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 17: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br><br>Reference 19: 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=124431687&amp;loc=d3e22583-107794<br><br>Reference 20: 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 21: 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 http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=SL5780133-109256<br><br>Reference 22: 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 23: 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=124431687&amp;loc=d3e22658-107794<br><br>Reference 24: 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=124509347&amp;loc=SL7669619-108580<br><br>Reference 25: 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=123359005&amp;loc=d3e8924-108599<br><br>Reference 26: 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=124431687&amp;loc=d3e22694-107794<br><br>Reference 27: 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=124431687&amp;loc=d3e22694-107794<br><br>Reference 28: 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 http://asc.fasb.org/extlink&amp;oid=109222650&amp;loc=SL51721683-107760<br><br>Reference 29: 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=124509347&amp;loc=SL7669625-108580<br><br>Reference 30: http://www.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=123359005&amp;loc=d3e8736-108599<br><br>Reference 31: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 32: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 33: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 34: http://www.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=123359005&amp;loc=d3e8906-108599<br><br>Reference 35: http://www.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=123359005&amp;loc=d3e8933-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_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_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=123359005&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=123359005&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=123359005&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=123359005&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=123359005&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=123367319&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_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=123359005&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=123359005&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=123359005&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=123359005&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=123359005&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=123351226&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=123359005&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=123359005&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=123359005&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=123351226&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=123367319&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=124432515&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&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=124432515&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&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>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=us-gaap_ProductMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_ProductMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeAgreementRevenueMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</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_EplontersenJointDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_EplontersenJointDevelopmentRevenueMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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>15
<FILENAME>R5.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624044004424">
<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, 2022</div></th>
<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_StatementOfIncomeAndComprehensiveIncomeAbstract', window );"><strong>CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (65,165)<span></span>
</td>
<td class="num">$ (89,869)<span></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_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax', window );">Unrealized losses on debt securities, net of tax</a></td>
<td class="num">(15,756)<span></span>
</td>
<td class="num">(3,006)<span></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_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Currency translation adjustment</a></td>
<td class="num">(154)<span></span>
</td>
<td class="num">(126)<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_us-gaap_ComprehensiveIncomeNetOfTax', window );">Comprehensive loss</a></td>
<td class="num">$ (81,075)<span></span>
</td>
<td class="num">$ (93,001)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ComprehensiveIncomeNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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, attributable to parent entity. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(24))<br> -URI http://asc.fasb.org/extlink&amp;oid=123367319&amp;loc=SL114868664-224227<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=124509347&amp;loc=d3e557-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(26))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124509347&amp;loc=SL7669625-108580<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=124509347&amp;loc=SL7669619-108580<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(18))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=124431353&amp;loc=SL124452729-227067<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 8: 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(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=123367319&amp;loc=SL114868664-224227<br><br>Reference 9: 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=123570139&amp;loc=d3e3602-108585<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 1<br> -Subparagraph (b)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22499-107794<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22663-107794<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 17: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br><br>Reference 19: 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=124431687&amp;loc=d3e22583-107794<br><br>Reference 20: 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 21: 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 http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=SL5780133-109256<br><br>Reference 22: 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 23: 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=124431687&amp;loc=d3e22658-107794<br><br>Reference 24: 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=124509347&amp;loc=SL7669619-108580<br><br>Reference 25: 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=123359005&amp;loc=d3e8924-108599<br><br>Reference 26: 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=124431687&amp;loc=d3e22694-107794<br><br>Reference 27: 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=124431687&amp;loc=d3e22694-107794<br><br>Reference 28: 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 http://asc.fasb.org/extlink&amp;oid=109222650&amp;loc=SL51721683-107760<br><br>Reference 29: 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=124509347&amp;loc=SL7669625-108580<br><br>Reference 30: http://www.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=123359005&amp;loc=d3e8736-108599<br><br>Reference 31: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 32: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 33: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 34: http://www.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=123359005&amp;loc=d3e8906-108599<br><br>Reference 35: http://www.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=123359005&amp;loc=d3e8933-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_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_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=123602790&amp;loc=d3e30304-110892<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 10<br> -Section 45<br> -Paragraph 9<br> -URI 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=124509347&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=124509347&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_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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=124509347&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=124509347&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_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>16
<FILENAME>R6.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624040776536">
<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</div></th>
</tr>
<tr class="rc">
<td class="pl custom" 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>
</tr>
<tr class="rc">
<td class="pl custom" 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>
</tr>
<tr class="re">
<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>
</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_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>
</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_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>
</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_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>
</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_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>
</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_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>
</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_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>
</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_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>
</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_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>
</tr>
<tr class="rc">
<td class="pl custom" 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>
</tr>
<tr class="rc">
<td class="pl custom" 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>
</tr>
<tr class="rc">
<td class="pl custom" 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, 2021</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">1,964,167<span></span>
</td>
<td class="num">(32,668)<span></span>
</td>
<td class="num">(1,159,903)<span></span>
</td>
<td class="nump">771,737<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl custom" 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, 2021</a></td>
<td class="nump">141,210<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</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_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">(65,165)<span></span>
</td>
<td class="num">(65,165)<span></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_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">(15,756)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(15,756)<span></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_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">(154)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(154)<span></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_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">1,848<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">1,849<span></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_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">847<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">26,236<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">26,236<span></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_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">(9,173)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(9,173)<span></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_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">(304)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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 custom" 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, 2022</a></td>
<td class="nump">$ 142<span></span>
</td>
<td class="nump">$ 1,983,078<span></span>
</td>
<td class="num">$ (48,578)<span></span>
</td>
<td class="num">$ (1,225,068)<span></span>
</td>
<td class="nump">$ 709,574<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl custom" 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, 2022</a></td>
<td class="nump">141,753<span></span>
</td>
<td class="text">&#160;<span></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=122142933&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=122142933&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=123468992&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_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(18))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=124431353&amp;loc=SL124452729-227067<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 8: 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(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=123367319&amp;loc=SL114868664-224227<br><br>Reference 9: 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=123570139&amp;loc=d3e3602-108585<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 1<br> -Subparagraph (b)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22499-107794<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22663-107794<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 17: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br><br>Reference 19: 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=124431687&amp;loc=d3e22583-107794<br><br>Reference 20: 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 21: 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 http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=SL5780133-109256<br><br>Reference 22: 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 23: 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=124431687&amp;loc=d3e22658-107794<br><br>Reference 24: 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=124509347&amp;loc=SL7669619-108580<br><br>Reference 25: 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=123359005&amp;loc=d3e8924-108599<br><br>Reference 26: 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=124431687&amp;loc=d3e22694-107794<br><br>Reference 27: 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=124431687&amp;loc=d3e22694-107794<br><br>Reference 28: 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 http://asc.fasb.org/extlink&amp;oid=109222650&amp;loc=SL51721683-107760<br><br>Reference 29: 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=124509347&amp;loc=SL7669625-108580<br><br>Reference 30: http://www.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=123359005&amp;loc=d3e8736-108599<br><br>Reference 31: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 32: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 33: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 34: http://www.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=123359005&amp;loc=d3e8906-108599<br><br>Reference 35: http://www.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=123359005&amp;loc=d3e8933-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_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=123454820&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=123454820&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=123602790&amp;loc=d3e30304-110892<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 10<br> -Section 45<br> -Paragraph 9<br> -URI 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=124509347&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=124509347&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=123467817&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=123467817&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_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=124436220&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 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://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 23<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124436220&amp;loc=d3e21914-107793<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 7<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22644-107794<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 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=124431353&amp;loc=SL124442411-227067<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 10<br> -Section 65<br> -Paragraph 4<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=122640432&amp;loc=SL121648383-210437<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 105<br> -SubTopic 10<br> -Section 65<br> -Paragraph 6<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=124434974&amp;loc=SL124442142-165695<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 105<br> -SubTopic 10<br> -Section 65<br> -Paragraph 6<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=124434974&amp;loc=SL124442142-165695<br><br>Reference 9: 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=123454820&amp;loc=SL4568740-111683<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 11: 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=123596393&amp;loc=d3e14064-108612<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 45<br> -Paragraph 5<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124436220&amp;loc=d3e21711-107793<br><br>Reference 13: 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 14: 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 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6450520&amp;loc=d3e32583-110901<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 65<br> -Paragraph 8<br> -Subparagraph (d)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=123459177&amp;loc=SL121830611-158277<br><br>Reference 17: 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 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 65<br> -Paragraph 8<br> -Subparagraph (d)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=123459177&amp;loc=SL121830611-158277<br><br>Reference 19: 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 (f)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br><br>Reference 20: 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 (f)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=121322162&amp;loc=SL121327923-165333<br><br>Reference 21: 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 4I<br> -URI http://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4590271-111686<br><br>Reference 22: 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 (f)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br><br>Reference 23: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 20<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32211-110900<br><br>Reference 24: 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 15<br> -URI http://asc.fasb.org/extlink&amp;oid=123454820&amp;loc=SL4568447-111683<br><br>Reference 25: 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 (f)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=121322162&amp;loc=SL121327923-165333<br><br>Reference 26: 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 1<br> -Subparagraph (b)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22499-107794<br><br>Reference 27: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 65<br> -Paragraph 15<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=121322162&amp;loc=SL121327923-165333<br><br>Reference 28: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 848<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Publisher FASB<br> -Subparagraph (a)(3)(iii)(03)<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>17
<FILENAME>R7.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624038908344">
<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, 2022</div></th>
<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_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 custom" 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="num">$ (65,165)<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_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 custom" 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">3,701<span></span>
</td>
<td class="nump">3,917<span></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_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense', window );">Amortization of right-of-use operating lease assets</a></td>
<td class="nump">602<span></span>
</td>
<td class="nump">394<span></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_us-gaap_AmortizationOfIntangibleAssets', window );">Amortization of patents</a></td>
<td class="nump">592<span></span>
</td>
<td class="nump">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_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments', window );">Amortization of premium on investments, net</a></td>
<td class="nump">4,175<span></span>
</td>
<td class="nump">4,023<span></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_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="nump">1,343<span></span>
</td>
<td class="nump">860<span></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_us-gaap_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="nump">26,236<span></span>
</td>
<td class="nump">37,861<span></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_us-gaap_RealizedInvestmentGainsLosses', window );">Gain on investments</a></td>
<td class="num">(10)<span></span>
</td>
<td class="num">(13)<span></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_us-gaap_GainLossOnDispositionOfAssets', window );">Non-cash losses related to disposal of property, plant and equipment</a></td>
<td class="nump">527<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived', window );">Non-cash losses related to patents</a></td>
<td class="nump">110<span></span>
</td>
<td class="nump">221<span></span>
</td>
</tr>
<tr class="re">
<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 custom" 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">35,774<span></span>
</td>
<td class="nump">52,807<span></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_us-gaap_IncreaseDecreaseInInventories', window );">Inventories</a></td>
<td class="nump">774<span></span>
</td>
<td class="num">(234)<span></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_us-gaap_IncreaseDecreaseInOtherOperatingAssets', window );">Other current and long-term assets</a></td>
<td class="num">(7,222)<span></span>
</td>
<td class="nump">16,481<span></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_us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable', window );">Income taxes receivable</a></td>
<td class="nump">865<span></span>
</td>
<td class="nump">2<span></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_us-gaap_IncreaseDecreaseInAccountsPayable', window );">Accounts payable</a></td>
<td class="nump">2,878<span></span>
</td>
<td class="num">(9,569)<span></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_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities', window );">Accrued compensation</a></td>
<td class="num">(22,285)<span></span>
</td>
<td class="num">(36,465)<span></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_us-gaap_IncreaseDecreaseInOtherCurrentLiabilities', window );">Accrued liabilities and other current liabilities</a></td>
<td class="nump">10,473<span></span>
</td>
<td class="num">(11,905)<span></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_us-gaap_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="num">(25,018)<span></span>
</td>
<td class="num">(23,717)<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_us-gaap_NetCashProvidedByUsedInOperatingActivities', window );">Net cash used in operating activities</a></td>
<td class="num">(31,650)<span></span>
</td>
<td class="num">(54,662)<span></span>
</td>
</tr>
<tr class="re">
<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 custom" 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">(462,855)<span></span>
</td>
<td class="num">(330,051)<span></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_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities', window );">Proceeds from sale of short-term investments</a></td>
<td class="nump">178,837<span></span>
</td>
<td class="nump">411,907<span></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_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment', window );">Purchases of property, plant and equipment</a></td>
<td class="num">(2,705)<span></span>
</td>
<td class="num">(1,772)<span></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_us-gaap_PaymentsToAcquireIntangibleAssets', window );">Acquisition of licenses and other assets, net</a></td>
<td class="num">(826)<span></span>
</td>
<td class="num">(1,228)<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_us-gaap_NetCashProvidedByUsedInInvestingActivities', window );">Net cash (used in) provided by investing activities</a></td>
<td class="num">(287,549)<span></span>
</td>
<td class="nump">78,856<span></span>
</td>
</tr>
<tr class="re">
<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 custom" 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">1,848<span></span>
</td>
<td class="nump">7,760<span></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_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">(9,173)<span></span>
</td>
<td class="num">(15,337)<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_us-gaap_NetCashProvidedByUsedInFinancingActivities', window );">Net cash used in financing activities</a></td>
<td class="num">(7,325)<span></span>
</td>
<td class="num">(7,577)<span></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_us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents', window );">Effects of exchange rates on cash</a></td>
<td class="num">(154)<span></span>
</td>
<td class="num">(126)<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_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect', window );">Net (decrease) increase in cash and cash equivalents</a></td>
<td class="num">(326,678)<span></span>
</td>
<td class="nump">16,491<span></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_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of period</a></td>
<td class="nump">869,191<span></span>
</td>
<td class="nump">397,664<span></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_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at end of period</a></td>
<td class="nump">542,513<span></span>
</td>
<td class="nump">414,155<span></span>
</td>
</tr>
<tr class="re">
<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="ro">
<td class="pl custom" 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">594<span></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_us-gaap_IncomeTaxesPaid', window );">Income taxes paid</a></td>
<td class="nump">2<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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="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_NonCashCapitalAndPatentExpenditures', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="nump">$ 1,344<span></span>
</td>
<td class="nump">$ 1,876<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=123570139&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=123570139&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=123367319&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1F<br> -Subparagraph (b)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495355-112611<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=124435984&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=123570139&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=123570139&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=123570139&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=123431023&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=123444420&amp;loc=d3e33268-110906<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI http://asc.fasb.org/extlink&amp;oid=123570139&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_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=123570139&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=123444420&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_GainLossOnDispositionOfAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 gain (loss) on sale or disposal of property, plant and equipment assets, excluding oil and gas property and timber property.</p></div>
<a href="javascript:void(0);" onclick="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=123570139&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=123351718&amp;loc=d3e2443-110228<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=109226691&amp;loc=d3e2941-110230<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnDispositionOfAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=123570139&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=123431023&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=123570139&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=123570139&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=123570139&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=123570139&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=123570139&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 912<br> -SubTopic 310<br> -Section 45<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123371682&amp;loc=d3e55415-109406<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><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=123570139&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=123570139&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=123570139&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=123570139&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=123431023&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=123570139&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=123570139&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=123570139&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=123570139&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=123570139&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=123570139&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=123570139&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_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI http://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(18))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=124431353&amp;loc=SL124452729-227067<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 8: 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(20))<br> -URI http://asc.fasb.org/extlink&amp;oid=123367319&amp;loc=SL114868664-224227<br><br>Reference 9: 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=123570139&amp;loc=d3e3602-108585<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 1<br> -Subparagraph (b)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22499-107794<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(i))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22663-107794<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iv))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 17: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br><br>Reference 19: 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=124431687&amp;loc=d3e22583-107794<br><br>Reference 20: 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 21: 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 http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=SL5780133-109256<br><br>Reference 22: 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 23: 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=124431687&amp;loc=d3e22658-107794<br><br>Reference 24: 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=124509347&amp;loc=SL7669619-108580<br><br>Reference 25: 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=123359005&amp;loc=d3e8924-108599<br><br>Reference 26: 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=124431687&amp;loc=d3e22694-107794<br><br>Reference 27: 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=124431687&amp;loc=d3e22694-107794<br><br>Reference 28: 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 http://asc.fasb.org/extlink&amp;oid=109222650&amp;loc=SL51721683-107760<br><br>Reference 29: 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=124509347&amp;loc=SL7669625-108580<br><br>Reference 30: http://www.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=123359005&amp;loc=d3e8736-108599<br><br>Reference 31: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(5))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442526-122756<br><br>Reference 32: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 33: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI http://asc.fasb.org/extlink&amp;oid=124359900&amp;loc=SL124442552-122756<br><br>Reference 34: http://www.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=123359005&amp;loc=d3e8906-108599<br><br>Reference 35: http://www.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=123359005&amp;loc=d3e8933-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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=123570139&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_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=123570139&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=123570139&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=123570139&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=124260329&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_PaymentsToAcquireIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 acquire asset without physical form usually arising from contractual or other legal rights, excluding goodwill.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div 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=123570139&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_PaymentsToAcquireIntangibleAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=123570139&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=123570139&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=123570139&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=123570139&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=124260329&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_RealizedInvestmentGainsLosses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 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 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04.3(a))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RealizedInvestmentGainsLosses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=123570139&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>
</tr>
<tr>
<td><strong> Balance 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>18
<FILENAME>R8.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624042980328">
<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>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Basis of Presentation [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_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock', window );">Basis of Presentation</a></td>
<td class="text">
<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;">We prepared the unaudited interim condensed consolidated financial statements for the three months ended&#160;March 31, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. 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 December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our 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;).</div>
<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_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</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_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<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>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>19
<FILENAME>R9.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624043031832">
<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, 2022</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 custom" 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;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. If there is no appropriate analogous authoritative accounting literature, ASC 808 suggests companies consistently apply a reasonable and rational accounting policy election. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.</div>

<div><br/></div>

<div style="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 January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: 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 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for collaborations with substantive changes that occurred in 2022. 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, 2021 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;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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>
  </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;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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" 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.</div>

<div><br/></div>

<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" 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 first quarter of 2022, we earned a $10 million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#8217;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated future product sales;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated royalties we may receive from future product sales;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated expenses we may incur;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated income taxes; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A discount rate.</div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" 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 number of internal hours we will spend performing these services;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work we will perform;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work that we will contract with third parties to perform; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" 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: justify; 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;">Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our 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; 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;">Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.</div>

<div><br/></div>

<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 agreements 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. Under our agreements with Sobi, we transferred all reserves to Sobi. 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, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.</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 and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. 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: left; 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 2021, 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 first quarter of 2022, we recognized $18 million in milestone payments when Biogen advanced two targets under our 2013 strategic collaboration. 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 first quarter of 2022.</div>

<div><br/></div>

<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 2021, we earned a $60 million license fee from Biogen when Biogen licensed ION306, an investigational medicine in development to treat SMA.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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. For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.</div>

<div><br/></div>

<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;">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" 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" 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: left; 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" 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" 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" 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>

<div><br/></div>

<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;">Eplontersen Collaboration with AstraZeneca</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had one performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. As we continue to lead the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively. Refer to Item 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations</span>, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. </div>

<div><br/></div>

<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, 2022, approximately 82.2 percent of our contracts receivables were from two significant customers. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two significant customers.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-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>

<div><br/></div>

<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;">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, 2022 and 2021, we recognized $26.2 million and $26.0 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>

<div><br/></div>

<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>

<div><br/></div>

<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, 2022, we held equity investments in three publicly held companies, Antisense Therapeutics Limited, or ATL, Bicycle Therapeutics plc, or Bicycle, and ProQR Therapeutics N.V., or ProQR. We also held equity investments in seven privately held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, YourBio Health, Inc. (formerly 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 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. As a result of these observable price changes, we recognized a total gain of $14.8 million on our investments in these companies 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. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We recorded an immaterial amount of inventory write-offs for the three months ended&#160;March 31, 2022 and 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,507</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- commercial</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,165</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,139</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,929</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,637</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,770</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">466</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">390</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,032</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,806</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

<div style="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 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="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $9.6 million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.</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 expected to be realized.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.</div>

<div><br/></div>

<div style="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="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;">Basic and Diluted Net Loss Per Share</div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the three months ended&#160;March 31, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended March 31, 2022 and 2021 were $0.46 and $0.64, respectively.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-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, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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, or 0.125% Notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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% Notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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" 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" 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" 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three months ended&#160;March 31, 2021, common stock from our 1 percent convertible senior notes, or 1% Notes, would also have had an anti-dilutive effect on net loss per share.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three months ended&#160;March 31, 2022, common stock from the following would also have had an anti-dilutive effect on net loss per share:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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 percent convertible senior notes, or 0% Notes; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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% Notes.</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, 2022, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>

<div><br/></div>

<div style="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;">We account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability on our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our 0% and 0.125% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our 0% and 0.125% Notes over the respective contractual term using an effective interest rate of 0.5 percent for each note. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible Debt</span>, for further details on our convertible debt instruments.</div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our 0% Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the 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;">We operate as a <span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e">single</span> segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.</div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our 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.</div>

<div><br/></div>

<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, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">55.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: 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;">6.3 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the three months ended March 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</div></td>
  </tr>
</table>

<div><br/></div>

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

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">0.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">50.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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, 2022 was $33.08 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 PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other executive officers. 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 the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our executive officers for the three months ended&#160;March 31, 2022 and 2021 were $42.28 and $77.17 per share, 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 table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2022 and 2021 (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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">160</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">19,082</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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>
  </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;">6,994</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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>
  </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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,236</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2022, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $67.7 million, $69.2 million and $5.4 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, 1.7 years and 1.6 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;">We do not expect any recently issued accounting standards to have a material impact to our financial results.</div>
<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_AccountingPoliciesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</tr>
<tr>
<td style="padding-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_SignificantAccountingPoliciesTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for all significant accounting policies of the reporting entity.</p></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 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=123372394&amp;loc=d3e18726-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -URI http://asc.fasb.org/topic&amp;trid=2122369<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SignificantAccountingPoliciesTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>20
<FILENAME>R10.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624043007240">
<tr>
<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>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsAbstract', window );"><strong>Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentTextBlock', window );">Investments</a></td>
<td class="text">
<div style="text-align: 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, 2022:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">One year</span> or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">one year</span> but within <span style="text-indent: 0pt;">two years</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">two years</span> but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797">three and a half years</span></span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div></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>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at March 31, 2022, 93 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, 2022, we had an ownership interest of less than 20 percent in seven private companies and three public companies with which we conduct business. The privately held companies are Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, YourBio Health, Inc. and Suzhou-Ribo Life Science Co, Ltd. The publicly traded companies are Antisense Therapeutics Ltd., Bicycle and ProQR.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>

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

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;">Amortized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">March 31, 2022</span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 (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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">420,081</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">131</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,766</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">418,446</div></td>
    <td colspan="1" style="text-align: 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;">34,407</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">(49</div></td>
    <td colspan="1" style="text-align: left; 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;">34,358</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 (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">330,358</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,133</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">329,226</div></td>
    <td colspan="1" style="text-align: 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;">158,548</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(376</div></td>
    <td colspan="1" style="text-align: left; 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;">158,173</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;">6,419</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">(99</div></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;">6,320</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">949,813</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">133</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;">(3,423</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;">946,523</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;">345,813</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,275</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="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;">335,562</div></td>
    <td colspan="1" style="text-align: 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;">72,844</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,974</div></td>
    <td colspan="1" style="text-align: left; 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;">70,870</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;">164,040</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,544</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="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;">161,566</div></td>
    <td colspan="1" style="text-align: 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;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="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;">34,995</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;">(818</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;">34,177</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 securities with a maturity of more than one year</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">617,692</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">94</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">(15,611</div></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;">602,175</div></td>
    <td 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: 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;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,567,505</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">227</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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(19,034</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,548,698</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;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">3,946</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,274</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">11,569</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;">Total equity securities included in deposits and other assets (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,115</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,822</div></td>
    <td 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 equity securities</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;">35,012</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;">20,653</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,274</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;">51,391</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: 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; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,602,517</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,880</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(23,308</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,600,089</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;">Amortized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">December 31, 2021</span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383,870</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">728</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(226</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384,372</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" 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;">48,493</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18</div></td>
    <td colspan="1" style="text-align: left; 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;">48,494</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 (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,424</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(64</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,360</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,770</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;">45</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;">(37</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;">134,778</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 securities with a maturity of one year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">612,557</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">792</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(345</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">613,004</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">382,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,644</div></td>
    <td colspan="1" style="text-align: left; 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;">379,687</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 U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,935</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(561</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,374</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,635</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(500</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="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;">137,274</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,909</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(224</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,686</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,136</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;">(37</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;">6,099</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 securities with a maturity of more than one year</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">638,615</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">471</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,966</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">635,120</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,251,172</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,263</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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,311</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,248,124</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;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,145</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">18,205</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;">Total equity securities included in deposits and other assets (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,615</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,322</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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;" valign="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;">27,512</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;">23,852</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;">(837</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;">50,527</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: 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; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,278,684</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,115</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,148</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,298,651</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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;">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" 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;">Our equity securities included in other current assets consisted of our investments in two publicly traded companies, ProQR and Bicycle, which we classify as Level 1 and Level 3 investments, respectively. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2022, we recognized a $3.4 million and a $3.2 million unrealized loss on our condensed consolidated statement of operations related to our investments in ProQR and Bicycle, respectively. In the three months ended March 31, 2021, our equity securities included in other current assets only consisted of ProQR.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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;"><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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands, except for number of investments). We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 12 Months of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">337</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">647,390</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,694</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,300</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(347</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">658,690</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(12,041</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14</div></td>
    <td colspan="1" style="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;">95,543</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,697</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,685</div></td>
    <td colspan="1" style="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;">(326</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105,228</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,023</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">406,747</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,539</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,860</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">(138</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <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;">411,607</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,677</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">619</div></td>
    <td colspan="1" style="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;">173,537</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,096</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,455</div></td>
    <td colspan="1" style="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;">(98</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,992</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,194</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">1,315</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">(16</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,005</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; 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;">(83</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,320</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">(99</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,017</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,324,532</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18,042</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36,305</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(992</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,360,837</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(19,034</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>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for investment.</p></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 321<br> -URI http://asc.fasb.org/topic&amp;trid=75115024<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -URI http://asc.fasb.org/topic&amp;trid=2196928<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 325<br> -URI http://asc.fasb.org/topic&amp;trid=2197064<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -URI http://asc.fasb.org/topic&amp;trid=2196965<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_InvestmentsAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>21
<FILENAME>R11.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624044398328">
<tr>
<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>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [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_us-gaap_FairValueDisclosuresTextBlock', window );">Fair Value Measurements</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4.&#160; Fair Value Measurements</div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at March 31, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of March 31, 2022 and December 31, 2021, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our Bicycle investment was subject to trading restrictions that extend to the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.</span> The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">March 31, 2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">407,399</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">407,399</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">754,008</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">754,008</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (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;">105,228</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">105,228</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">490,792</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">490,792</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (5)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">192,350</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">192,350</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (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;">6,320</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">6,320</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></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><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in Bicycle Therapeutics plc (6)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,131</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,131</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (6)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">438</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;">438</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,967,666</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">898,629</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,057,906</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,131</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><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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, 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;">Quoted Prices in</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">541,199</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">541,199</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">764,059</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">764,059</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (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;">120,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (7)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (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;">6,099</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></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><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in Bicycle Therapeutics plc (6)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (6)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,875</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;">3,875</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,807,528</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">727,708</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,065,490</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</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="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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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" 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;">$13.5 million was 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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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;">$15.0 million was 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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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;">$10.3 million was 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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in other current assets on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$2.3 million was 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>
  </tr>
</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><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 0.125% Notes and 0% Notes had a fair value of $494.4 million and $595.4 million at March 31, 2022, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div>
<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_FairValueDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_FairValueDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-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_FairValueDisclosuresTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired information.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=123874694&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_FairValueDisclosuresTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>22
<FILENAME>R12.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624043051784">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [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_us-gaap_IncomeTaxDisclosureTextBlock', window );">Income Taxes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; 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;">Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over five years pursuant to Internal Revenue Code, or IRC, Section 174. Although the U.S. Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified. As a result, we recorded a $1.1 million income tax expense for the three months ended&#160;March 31, 2022 compared to $0.1 million income tax expense for the same period in 2021. </div>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxDisclosureTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for income taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -URI http://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32857-109319<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 2<br> -Subparagraph (SAB Topic 11.C)<br> -URI http://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330215-122817<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32809-109319<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.5.Q1)<br> -URI http://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 14<br> -URI http://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32705-109319<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 270<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6424409&amp;loc=d3e44925-109338<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -URI http://asc.fasb.org/topic&amp;trid=2144680<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=6424122&amp;loc=d3e41874-109331<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -URI 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_IncomeTaxDisclosureTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>23
<FILENAME>R13.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624043079272">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndLicensingAgreementsAbstract', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_CollaborativeArrangementDisclosureTextBlock', window );">Collaborative Arrangements and Licensing Agreements</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6.&#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;">2022</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, 2021</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 numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, Angelman Syndrome, 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, 2022, we have received $3.3 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, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties (commercial revenue)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">40.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="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>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue from our relationship with Biogen</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">78.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><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>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66</div></td>
    <td colspan="1" style="text-align: left; 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;">70</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our condensed consolidated balance sheet at March 31, 2022 and December 31, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>included deferred revenue of $385.5 million and $407.5 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 quarter of 2022, we did not have any material 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 the first quarter of 2022, we earned $18 million in milestone payments from Biogen when Biogen advanced two targets under our 2013 strategic collaboration. We recognized the milestone payments in full in the first quarter of 2022 because we did not have any remaining performance obligations related to the milestone payments. We will achieve the next payment of up to $10 million if Biogen advances a medicine under our 2013 strategic neurology collaboration.</div>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementsAndLicensingAgreementsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsAbstract</td>
</tr>
<tr>
<td style="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_CollaborativeArrangementDisclosureTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<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>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CollaborativeArrangementDisclosureTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>24
<FILENAME>R14.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624044395544">
<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, 2022</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>
</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_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;">7. 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% Notes to repurchase $247.9 million in principal of our 1% Notes for $257.0 million.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2022, 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>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.6</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; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde">April 2026</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.84</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.39</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our 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: 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, 2022, 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>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec">December 2024</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.28</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">123.38</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

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

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our 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;">In April 2021, we repurchased $247.9 million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $8.6 million non-cash loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our 1% Notes. The non-cash loss on the early retirement of our debt is the difference between the amount paid to retire our 1% Notes and the net carrying balance of the liability at the time that we retired the debt. We paid the remaining principal balance of our 1% Notes with $62.0 million of cash at maturity in November 2021.</div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 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 </span>100 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.</span> The 1% Notes were subject to similar terms.</div>
<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_DebtDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_DebtDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-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_DebtDisclosureTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for information about short-term and long-term debt arrangements, which includes amounts of borrowings under each line of credit, note payable, commercial paper issue, bonds indenture, debenture issue, own-share lending arrangements and any other contractual agreement to repay funds, and about the underlying arrangements, rationale for a classification as long-term, including repayment terms, interest rates, collateral provided, restrictions on use of assets and activities, whether or not in compliance with debt covenants, and other matters important to users of the financial statements, such as the effects of refinancing and noncompliance with debt covenants.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div 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> -URI http://asc.fasb.org/topic&amp;trid=2208564<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1C<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495334-112611<br><br>Reference 4: 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 1I<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495371-112611<br><br>Reference 5: 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 1I<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495371-112611<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(c))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (g)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 8: 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 1C<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495334-112611<br><br>Reference 9: 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 1C<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495334-112611<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495348-112611<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 12: 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 1I<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495371-112611<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (i)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtDisclosureTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>25
<FILENAME>R15.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624038503352">
<tr>
<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>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Basis of Presentation [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_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;">We prepared the unaudited interim condensed consolidated financial statements for the three months ended&#160;March 31, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. 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 December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConsolidationPolicyTextBlock', window );">Consolidation</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 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;).</div>
<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_BasisOfAccountingPolicyPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_BasisOfAccountingPolicyPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConsolidationPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123372394&amp;loc=d3e18823-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=d3e5614-111684<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConsolidationPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>26
<FILENAME>R16.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624038515112">
<tr>
<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, 2022</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 custom" 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;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. If there is no appropriate analogous authoritative accounting literature, ASC 808 suggests companies consistently apply a reasonable and rational accounting policy election. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.</div>

<div><br/></div>

<div style="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 January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: 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 6, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for collaborations with substantive changes that occurred in 2022. 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, 2021 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;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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>
  </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;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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" 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.</div>

<div><br/></div>

<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" 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 first quarter of 2022, we earned a $10 million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#8217;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated future product sales;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated royalties we may receive from future product sales;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated expenses we may incur;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated income taxes; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A discount rate.</div></td>
  </tr>
</table>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We typically estimate the selling price of R&amp;D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" 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 number of internal hours we will spend performing these services;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work we will perform;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work that we will contract with third parties to perform; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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" 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: justify; 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;">Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;A, expenses in our 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; 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;">Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.</div>

<div><br/></div>

<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 agreements 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. Under our agreements with Sobi, we transferred all reserves to Sobi. 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, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.</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 and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services. 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: left; 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 2021, 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 first quarter of 2022, we recognized $18 million in milestone payments when Biogen advanced two targets under our 2013 strategic collaboration. 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 first quarter of 2022.</div>

<div><br/></div>

<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 2021, we earned a $60 million license fee from Biogen when Biogen licensed ION306, an investigational medicine in development to treat SMA.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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. For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.</div>

<div><br/></div>

<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;">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" 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" 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: left; 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" 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" 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" 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>

<div><br/></div>

<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;">Eplontersen Collaboration with AstraZeneca</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had one performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. As we continue to lead the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively. Refer to Item 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis of Financial Condition and Results of Operations</span>, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. </div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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, 2022, approximately 82.2 percent of our contracts receivables were from two significant customers. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two significant customers.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" 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>
<span></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_us-gaap_RevenueRecognitionPolicyTextBlock', window );">Deferred Revenue</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;">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, 2022 and 2021, we recognized $26.2 million and $26.0 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>
<span></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_us-gaap_CostOfSalesPolicyTextBlock', window );">Cost of Sales</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;">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>
<span></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_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, 2022, we held equity investments in three publicly held companies, Antisense Therapeutics Limited, or ATL, Bicycle Therapeutics plc, or Bicycle, and ProQR Therapeutics N.V., or ProQR. We also held equity investments in seven privately held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, YourBio Health, Inc. (formerly 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 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. As a result of these observable price changes, we recognized a total gain of $14.8 million on our investments in these companies in our condensed consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We recorded an immaterial amount of inventory write-offs for the three months ended&#160;March 31, 2022 and 2021.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,507</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- commercial</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,165</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,139</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,929</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,637</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,770</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">466</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">390</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,032</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,806</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" 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 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="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $9.6 million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" 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 custom" 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 expected to be realized.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" 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 custom" 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 custom" 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="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;">Basic and Diluted Net Loss Per Share</div>

<div><br/></div>

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

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the three months ended&#160;March 31, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended March 31, 2022 and 2021 were $0.46 and $0.64, respectively.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-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, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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, or 0.125% Notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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% Notes;</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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" 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" 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" 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three months ended&#160;March 31, 2021, common stock from our 1 percent convertible senior notes, or 1% Notes, would also have had an anti-dilutive effect on net loss per share.</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the three months ended&#160;March 31, 2022, common stock from the following would also have had an anti-dilutive effect on net loss per share:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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 percent convertible senior notes, or 0% Notes; and</div></td>
  </tr>
</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 36pt;"/>
    <td style="width: 18pt; vertical-align: top; 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% Notes.</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, 2022, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" 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;">We account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability on our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our 0% and 0.125% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our 0% and 0.125% Notes over the respective contractual term using an effective interest rate of 0.5 percent for each note. Refer to Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible Debt</span>, for further details on our convertible debt instruments.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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% Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the 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 custom" 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;">We operate as a <span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e">single</span> segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our 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.</div>

<div><br/></div>

<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, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:</div>

<div><br/></div>

<div style="display:none;"><br/></div>
<div style="text-align: 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">55.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: 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;">6.3 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the three months ended March 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</div></td>
  </tr>
</table>

<div><br/></div>

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

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">0.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">50.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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, 2022 was $33.08 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 PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other executive officers. 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 the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our executive officers for the three months ended&#160;March 31, 2022 and 2021 were $42.28 and $77.17 per share, 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 table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2022 and 2021 (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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">160</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">19,082</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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>
  </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;">6,994</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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>
  </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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,236</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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>
  </tr>
</table>

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

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of March 31, 2022, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $67.7 million, $69.2 million and $5.4 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, 1.7 years and 1.6 years, respectively.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Impact of Recently Issued Accounting Standards</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;">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;">We do not expect any recently issued accounting standards to have a material impact to our financial results.</div>
<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_AccountingPoliciesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</tr>
<tr>
<td style="padding-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_CostOfSalesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostOfSalesPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 related to debt. Includes, but is not limited to, debt issuance costs, the effects of refinancings, method of amortizing debt issuance costs and original issue discount, and classifications of debt.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=123465755&amp;loc=d3e1835-112601<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DerivativesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 its derivative instruments and hedging activities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=d3e41620-113959<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=d3e41638-113959<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=SL5579245-113959<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=d3e41675-113959<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(n))<br> -URI http://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=SL5579240-113959<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DerivativesPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerSharePolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 computing basic and diluted earnings or loss per share for each class of common stock and participating security. Addresses all significant policy factors, including any antidilutive items that have been excluded from the computation and takes into account stock dividends, splits and reverse splits that occur after the balance sheet date of the latest reporting period but before the issuance of the financial statements.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3630-109257<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerSharePolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for the impairment and disposal of long-lived assets including goodwill and other intangible assets.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 income taxes, which may include its accounting policies for recognizing and measuring deferred tax assets and liabilities and related valuation allowances, recognizing investment tax credits, operating loss carryforwards, tax credit carryforwards, and other carryforwards, methodologies for determining its effective income tax rate and the characterization of interest and penalties in the financial statements.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -URI http://asc.fasb.org/extlink&amp;oid=123427490&amp;loc=d3e32247-109318<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32847-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 19<br> -URI http://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32840-109319<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=124431353&amp;loc=SL116659661-227067<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI http://asc.fasb.org/extlink&amp;oid=123427490&amp;loc=d3e32280-109318<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32809-109319<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IntangibleAssetsFiniteLivedPolicy">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for finite-lived intangible assets. This accounting policy also might address: (1) the amortization method used; (2) the useful lives of such assets; and (3) how the entity assesses and measures impairment of such assets.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://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)<br> -URI http://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 920<br> -SubTopic 350<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120155617&amp;loc=SL120155638-234783<br><br>Reference 4: 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 (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=123372394&amp;loc=d3e18823-107790<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 920<br> -SubTopic 350<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=120155617&amp;loc=SL120155628-234783<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 920<br> -SubTopic 350<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120155617&amp;loc=SL120155628-234783<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<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>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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 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 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 912<br> -SubTopic 330<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6471895&amp;loc=d3e55923-109411<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=124437754&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://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=123372394&amp;loc=d3e18823-107790<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 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>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=123408670&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>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ReceivablesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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://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=123577603&amp;loc=d3e5033-111524<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10178-111534<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10149-111534<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI 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>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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 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>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=123351226&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=123351226&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=123351226&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=123351226&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=123351226&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=123372394&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=123351226&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=123351226&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=123351226&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>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=123372394&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=123372394&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>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SegmentReportingPolicyPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for segment reporting.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (e)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8864-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8864-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8864-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8864-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8864-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&amp;loc=d3e8864-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingPolicyPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for award under share-based payment arrangement. Includes, but is not limited to, methodology and assumption used in measuring cost.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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 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> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5047-113901<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_ShareBasedCompensationOptionAndIncentivePlansPolicy</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for treatment of receivables that are billable but have not been billed as of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -URI http://asc.fasb.org/topic&amp;trid=2196771<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UseOfEstimates">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for the use of estimates in the preparation of financial statements in conformity with generally accepted accounting principles.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6191-108592<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6161-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6143-108592<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e5967-108592<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6061-108592<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6132-108592<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e5967-108592<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_UseOfEstimates</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>27
<FILENAME>R17.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624044455192">
<tr>
<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>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ScheduleOfInventoryCurrentTableTextBlock', window );">Inventory</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-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, 2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,764</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,507</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"><div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- commercial</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,165</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,139</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,929</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,646</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,637</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,770</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">466</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">390</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"><div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,032</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,806</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">55.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: 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;">6.3 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 years</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the three months ended March 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">0.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">50.2</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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 custom" 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, 2022 and 2021 (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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">160</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
  </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;">19,082</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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>
  </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;">6,994</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; 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>
  </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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,236</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">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>
  </tr>
</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccountingPoliciesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</tr>
<tr>
<td style="padding-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_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of allocation of amount expensed and capitalized for award under share-based payment arrangement to statement of income or comprehensive income and statement of financial position. Includes, but is not limited to, corresponding line item in financial statement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div 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 (h)(1)<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.F)<br> -URI http://asc.fasb.org/extlink&amp;oid=122041274&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 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5047-113901<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_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ScheduleOfInventoryCurrentTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the carrying amount as of the balance sheet date of merchandise, goods, commodities, or supplies held for future sale or to be used in manufacturing, servicing or production 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 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(c))<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(6)(b))<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 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><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 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=6361739&amp;loc=d3e7789-107766<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ScheduleOfInventoryCurrentTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the significant assumptions used during the year to estimate the fair value of employee stock purchase plans, including, but not limited to: (a) expected term, (b) expected volatility of the entity's shares, (c) expected dividends, (d) risk-free rate(s), and (e) discount for post-vesting restrictions.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div 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)<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_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the significant assumptions used during the year to estimate the fair value of stock options, including, but not limited to: (a) expected term of share options and similar instruments, (b) expected volatility of the entity's shares, (c) expected dividends, (d) risk-free rate(s), and (e) discount for post-vesting restrictions.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div 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)<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_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>28
<FILENAME>R18.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624120732840">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsAbstract', window );"><strong>Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock', window );">Contract Maturity of Available-for-Sale Securities</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of March 31, 2022:</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">One year</span> or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">one year</span> but within <span style="text-indent: 0pt;">two years</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">two years</span> but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797">three and a half years</span></span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; 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">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div></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>
  </tr>
</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock', window );">Summary of Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>

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

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;">Amortized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">March 31, 2022</span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 (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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">420,081</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">131</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,766</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">418,446</div></td>
    <td colspan="1" style="text-align: 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;">34,407</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">(49</div></td>
    <td colspan="1" style="text-align: left; 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;">34,358</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 (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">330,358</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,133</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">329,226</div></td>
    <td colspan="1" style="text-align: 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;">158,548</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(376</div></td>
    <td colspan="1" style="text-align: left; 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;">158,173</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;">6,419</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">(99</div></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;">6,320</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: 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;">949,813</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">133</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;">(3,423</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;">946,523</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;">345,813</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,275</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="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;">335,562</div></td>
    <td colspan="1" style="text-align: 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;">72,844</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,974</div></td>
    <td colspan="1" style="text-align: left; 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;">70,870</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;">164,040</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,544</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="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;">161,566</div></td>
    <td colspan="1" style="text-align: 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;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="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;">34,995</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;">(818</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;">34,177</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 securities with a maturity of more than one year</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">617,692</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">94</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">(15,611</div></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;">602,175</div></td>
    <td 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: 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;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,567,505</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">227</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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(19,034</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,548,698</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;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">3,946</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,274</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">11,569</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;">Total equity securities included in deposits and other assets (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,115</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,822</div></td>
    <td 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 equity securities</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;">35,012</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;">20,653</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,274</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;">51,391</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: 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; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,602,517</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,880</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(23,308</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,600,089</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;">Amortized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">December 31, 2021</span></div></td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><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 (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383,870</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">728</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(226</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384,372</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" 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;">48,493</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18</div></td>
    <td colspan="1" style="text-align: left; 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;">48,494</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 (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,424</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(64</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,360</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,770</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;">45</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;">(37</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;">134,778</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 securities with a maturity of one year or less</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">612,557</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">792</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(345</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">613,004</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">382,000</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,644</div></td>
    <td colspan="1" style="text-align: left; 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;">379,687</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 U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,935</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(561</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,374</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" 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%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,635</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(500</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="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;">137,274</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,909</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(224</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,686</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,136</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;">(37</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;">6,099</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 securities with a maturity of more than one year</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">638,615</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">471</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,966</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">635,120</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,251,172</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,263</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"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,311</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">1,248,124</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;"><span style="text-decoration: underline;">Equity securities:</span></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,145</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">18,205</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;">Total equity securities included in deposits and other assets (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,615</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,707</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,322</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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;" valign="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;">27,512</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;">23,852</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;">(837</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;">50,527</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: 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; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,278,684</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,115</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,148</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,298,651</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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;">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" 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;">Our equity securities included in other current assets consisted of our investments in two publicly traded companies, ProQR and Bicycle, which we classify as Level 1 and Level 3 investments, respectively. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2022, we recognized a $3.4 million and a $3.2 million unrealized loss on our condensed consolidated statement of operations related to our investments in ProQR and Bicycle, respectively. In the three months ended March 31, 2021, our equity securities included in other current assets only consisted of ProQR.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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;"><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 custom" 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, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands, except for number of investments). We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</span></div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"><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;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 12 Months of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">337</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">647,390</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,694</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,300</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(347</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">658,690</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(12,041</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14</div></td>
    <td colspan="1" style="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;">95,543</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,697</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,685</div></td>
    <td colspan="1" style="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;">(326</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105,228</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,023</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">406,747</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,539</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,860</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">(138</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <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;">411,607</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,677</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">619</div></td>
    <td colspan="1" style="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;">173,537</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,096</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,455</div></td>
    <td colspan="1" style="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;">(98</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,992</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,194</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">1,315</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-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;">(16</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,005</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; 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;">(83</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,320</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <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;">(99</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,017</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,324,532</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18,042</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36,305</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(992</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,360,837</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">(19,034</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>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_InvestmentsAbstract</td>
</tr>
<tr>
<td style="padding-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_InvestmentsClassifiedByContractualMaturityDateTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of maturities of an entity's investments as well as any other information pertinent to the investments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of investments in an unrealized loss position for which other-than-temporary impairments have not been recognized in earnings (including investments for which a portion of an other-than-temporary impairment has been recognized in other comprehensive income), including: (a) the aggregate related fair value of investments with unrealized losses, (b) the aggregate amount of unrealized losses (that is, the amount by which amortized cost basis exceeds fair value).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div 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> -URI http://asc.fasb.org/extlink&amp;oid=123581744&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_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of unrealized gains and losses on investments.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>29
<FILENAME>R19.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624042970760">
<tr>
<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>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [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_us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock', window );">Assets Measured at Fair Value on a Recurring Basis</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at March 31, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of March 31, 2022 and December 31, 2021, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our Bicycle investment was subject to trading restrictions that extend to the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.</span> The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">March 31, 2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">407,399</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">407,399</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">754,008</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">754,008</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (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;">105,228</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">105,228</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (4)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">490,792</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">490,792</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (5)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">192,350</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-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;">192,350</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (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;">6,320</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="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;">6,320</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></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><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in Bicycle Therapeutics plc (6)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,131</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,131</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (6)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">438</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;">438</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,967,666</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">898,629</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,057,906</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,131</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><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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, 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;">Quoted Prices in</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">541,199</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">541,199</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">764,059</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">764,059</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (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;">120,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,868</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (3)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (7)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (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;">6,099</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></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><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in Bicycle Therapeutics plc (6)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"><div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment in ProQR Therapeutics N.V. (6)</div></div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,875</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;">3,875</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,807,528</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">727,708</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,065,490</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</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="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>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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" 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;">$13.5 million was 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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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;">$15.0 million was 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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; 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;">$10.3 million was 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>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in other current assets on our condensed consolidated balance sheet.</div></td>
  </tr>
</table>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">
  <tr>
    <td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7)</td>
    <td style="width: auto; vertical-align: top; text-align: justify;"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$2.3 million was 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>
  </tr>
</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of assets, including [financial] instruments measured at fair value that are classified in stockholders' equity, if any, by class that are measured at fair value on a recurring basis. The disclosures contemplated herein include the fair value measurements at the reporting date by the level within the fair value hierarchy in which the fair value measurements in their entirety fall, segregating fair value measurements using quoted prices in active markets for identical assets (Level 1), significant other observable inputs (Level 2), and significant unobservable inputs (Level 3).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div 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 (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123874694&amp;loc=d3e19207-110258<br><br>Reference 2: 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=123874694&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_FairValueAssetsMeasuredOnRecurringBasisTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FairValueDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_FairValueDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>30
<FILENAME>R20.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624042970200">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndLicensingAgreementsAbstract', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship with Biogen</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the three months ended March 31, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

<div><br/></div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"><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;">2022</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties (commercial revenue)</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 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;">40.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="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>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"><div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue from our relationship with Biogen</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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</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;">78.1</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: bottom; width: 76%;" valign="bottom"><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>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66</div></td>
    <td colspan="1" style="text-align: left; 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;">70</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div></td>
  </tr>
</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementsAndLicensingAgreementsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_CollaborativeArrangementsAndLicensingAgreementsAbstract</td>
</tr>
<tr>
<td style="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_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the nature of a concentration, a benchmark to which it is compared, and the percentage that the risk is to the benchmark.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: 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> -URI http://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br><br>Reference 4: 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 16<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6327-108592<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -URI http://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6442-108592<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_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>31
<FILENAME>R21.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624039361480">
<tr>
<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>
</tr>
<tr><th class="th"><div>Mar. 31, 2022</div></th></tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Notes [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ConvertibleDebtTableTextBlock', window );">Convertible Senior Notes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2022, 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>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12.6</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; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde">April 2026</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.84</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.39</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>

<div><br/></div>
<span></span>
</td>
</tr>
<tr class="rh">
<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>
</tr>
<tr 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_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Notes [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_us-gaap_ConvertibleDebtTableTextBlock', window );">Convertible Senior Notes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At March 31, 2022, 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>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">
  <tr>
    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"><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;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.0</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec">December 2024</span></div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div></td>
    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.28</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div></td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">123.38</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
  <tr>
    <td style="vertical-align: top; width: 88%;" valign="bottom"><div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div></td>
    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>
    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"><div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div></td>
    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>
  </tr>
</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ConvertibleNotesDisclosureLineItems">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ConvertibleNotesDisclosureLineItems</td>
</tr>
<tr>
<td style="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_ConvertibleDebtTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of convertible debt instrument. Includes, but is not limited to, principal amount and amortized premium or discount.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleDebtTableTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>32
<FILENAME>R22.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624035545160">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Revenue Recognition (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="6">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2022 </div>
<div>USD ($) </div>
<div>Target</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Component</div>
</th>
<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Component</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_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>
</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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 141,919<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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>
</tr>
<tr class="ro">
<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>
</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_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="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_Ion859Member', window );">ION859 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
</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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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_BiogenCollaboration2013StrategicNeurologyMember', window );">Biogen 2013 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
</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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 18,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_NumberOfTargetsAdvanced', window );">Number of targets advanced | Target</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember', window );">New Antisense Medicines for the Treatment of SMA [Member] | ION306 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
</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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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_AlnylamCollaborationMember', window );">Alnylam [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
</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_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">$ 41,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">IONIS-FB-L for Complement-Mediated Diseases [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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>
</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="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2018StrategicNeurologyMember', 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>
</tr>
<tr class="re">
<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>
</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="nump">$ 7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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_AstrazenecaCollaborationEplontersenMember', window );">Eplontersen Collaboration with AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
</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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfMaterialComponents', window );">Number of material components | Component</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner', window );">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</a></td>
<td class="nump">55.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_NumberOfMaterialComponents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMaterialComponents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTargetsAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 targets advanced under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTargetsAdvanced</td>
</tr>
<tr>
<td style="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_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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=123359005&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=123359005&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=123359005&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=123359005&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=123359005&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=123351226&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=123359005&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=123359005&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=123359005&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=123351226&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI http://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_BiogenIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_MajorCustomersAxis=ions_BiogenIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_Ion859Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_Ion859Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_BiogenCollaboration2013StrategicNeurologyMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_Ion306Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_Ion306Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_AlnylamCollaborationMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2018StrategicNeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_BiogenCollaboration2018StrategicNeurologyMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_AstrazenecaCollaborationEplontersenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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>33
<FILENAME>R23.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624036369064">
<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, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">2<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] | Two 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 custom" 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">82.20%<span></span>
</td>
<td class="nump">93.80%<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=123359005&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=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI 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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractReceivablesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_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>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>34
<FILENAME>R24.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624044602440">
<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, 2022</div></th>
<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_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 custom" 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">$ 26.2<span></span>
</td>
<td class="nump">$ 26.0<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=123351226&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityRevenueRecognized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>35
<FILENAME>R25.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624040606232">
<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="2">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2022 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($) </div>
<div>Investment</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_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>
</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">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl 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>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued', window );">Number of investments in privately held companies that were revalued | Investment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3<span></span>
</td>
</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_us-gaap_GainLossOnInvestments', window );">Gain on investments | $</a></td>
<td class="num">$ (6,625)<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember', window );">Investments in Dynacure, Suzhou-Ribo and 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>
</tr>
<tr class="re">
<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>
</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_us-gaap_GainLossOnInvestments', window );">Gain on investments | $</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 14,800<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Number of investments in privately-held companies that were revalued since the companies sold additional equity securities.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</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_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_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>
</tr>
<tr>
<td style="padding-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_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=123581744&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=123367319&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=123570139&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_FinancialInstrumentAxis=ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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>36
<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">
							function toggleNextSibling (e) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624038605096">
<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, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" 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">$ 17,929<span></span>
</td>
<td class="nump">$ 18,646<span></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_us-gaap_InventoryWorkInProcess', window );">Work in process</a></td>
<td class="nump">5,637<span></span>
</td>
<td class="nump">5,770<span></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_us-gaap_InventoryFinishedGoods', window );">Finished goods</a></td>
<td class="nump">466<span></span>
</td>
<td class="nump">390<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_us-gaap_InventoryNet', window );">Total inventory</a></td>
<td class="nump">24,032<span></span>
</td>
<td class="nump">24,806<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_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 custom" 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">15,764<span></span>
</td>
<td class="nump">14,507<span></span>
</td>
</tr>
<tr class="rh">
<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 custom" 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">$ 2,165<span></span>
</td>
<td class="nump">$ 4,139<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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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=124098289&amp;loc=d3e6676-107765<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 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_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>
</tr>
<tr>
<td style="padding-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_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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryWorkInProcess">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>37
<FILENAME>R27.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624120694040">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Leases (Details) - Office Space in Boston, Massachusetts [Member]<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th">
<div>Mar. 31, 2022 </div>
<div>USD ($)</div>
</th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_LesseeOperatingLeaseFreeRentPeriod', window );">Free rent period</a></td>
<td class="text">7 months<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Lease payments over sublease term</a></td>
<td class="nump">$ 9.6<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseFreeRentPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Period of time lessee will receive free rent under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseFreeRentPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI http://asc.fasb.org/extlink&amp;oid=123408670&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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>38
<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">
							function toggleNextSibling (e) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624043124360">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details) - $ / shares<br></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, 2022</div></th>
<th class="th"><div>Mar. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" 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">$ (0.46)<span></span>
</td>
<td class="num">$ (0.64)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
</tr>
<tr class="ro">
<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_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<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>
</tr>
<tr class="re">
<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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI 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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=d3e1448-109256<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 4<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<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 11<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=d3e1337-109256<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI http://asc.fasb.org/extlink&amp;oid=123482062&amp;loc=SL123482106-238011<br><br>Reference 9: 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=125512782&amp;loc=d3e4984-109258<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI http://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<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 55<br> -Paragraph 15<br> -URI http://asc.fasb.org/extlink&amp;oid=125512782&amp;loc=d3e3842-109258<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 7<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22644-107794<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 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<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=123367319&amp;loc=SL114868664-224227<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=d3e1252-109256<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=125511455&amp;loc=SL5780133-109256<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI 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>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasicAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</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>39
<FILENAME>R29.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624036369016">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Significant Accounting Policies, Convertible Debt (Details)<br></strong></div></th>
<th class="th"><div>Mar. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Mar. 31, 2021</div></th>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
</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_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></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_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>
</tr>
<tr class="rh">
<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>
</tr>
<tr class="ro">
<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>
</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_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</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_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>
</tr>
</table>
<div style="display: none;">
<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=123466204&amp;loc=SL6036836-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28551-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=124429444&amp;loc=SL124452920-239629<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI 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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI 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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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_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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>40
<FILENAME>R30.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624043046840">
<tr>
<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>
</tr>
<tr><th class="th">
<div>Mar. 31, 2022 </div>
<div>Segment</div>
</th></tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_NumberOfOperatingSegments', window );">Number of operating segments</a></td>
<td class="nump">1<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NumberOfOperatingSegments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 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=123359005&amp;loc=d3e8672-108599<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NumberOfOperatingSegments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>41
<FILENAME>R31.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624035956056">
<tr>
<th class="tl" colspan="2" 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, 2022 </div>
<div>USD ($) </div>
<div>Period </div>
<div>$ / shares </div>
<div>shares</div>
</th>
<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($) </div>
<div>$ / shares</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_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Non-cash stock-based compensation expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 26,236<span></span>
</td>
<td class="nump">$ 37,861<span></span>
</td>
</tr>
<tr class="rh">
<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="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_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Non-cash stock-based compensation expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">160<span></span>
</td>
<td class="nump">182<span></span>
</td>
</tr>
<tr class="rh">
<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_ResearchDevelopmentAndPatentExpensesMember', window );">Research, Development and Patent Expense [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_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Non-cash stock-based compensation expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">19,082<span></span>
</td>
<td class="nump">25,899<span></span>
</td>
</tr>
<tr class="rh">
<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="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_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Non-cash stock-based compensation expense</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6,994<span></span>
</td>
<td class="nump">$ 11,780<span></span>
</td>
</tr>
<tr class="rh">
<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="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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions', window );">Unrecognized compensation expense related to non-vested stock options</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 67,700<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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] | Employees [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1.70%<span></span>
</td>
<td class="nump">0.50%<span></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_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<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_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">55.20%<span></span>
</td>
<td class="nump">55.10%<span></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_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="text">6 years 3 months 18 days<span></span>
</td>
<td class="text">4 years 10 months 24 days<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member', window );">Stock Options Granted Prior to January 1, 2022 [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">7 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=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember', window );">Stock Options Granted on January 1, 2022 and Thereafter [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember', window );">ESPP [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.60%<span></span>
</td>
<td class="nump">0.10%<span></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_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<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_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">50.20%<span></span>
</td>
<td class="nump">39.10%<span></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_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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="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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 69,200<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member] | Minimum [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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] | Board of Directors [Member] | Maximum [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" 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="th" style="border-bottom: 0px;"><sup></sup></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] | Employees [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share) | $ / shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 33.08<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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="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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 5,400<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">1 year 7 months 6 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] | Executive Officers [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods', window );">Number of performance periods | Period</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" 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="th" style="border-bottom: 0px;"><sup></sup></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 (in shares) | shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share) | $ / shares</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 42.28<span></span>
</td>
<td class="nump">$ 77.17<span></span>
</td>
</tr>
<tr class="rh">
<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] | Executive Officers [Member] | Minimum [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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] | Executive Officers [Member] | Maximum [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl 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="th" style="border-bottom: 0px;"><sup></sup></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] | Executive Officers [Member] | One-Year Period [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></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] | Executive Officers [Member] | Two-Year Period [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" 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="th" style="border-bottom: 0px;"><sup></sup></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] | Executive Officers [Member] | Three-Year Period [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">33.30%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="3"></td></tr>
<tr><td colspan="3"><table class="outerFootnotes" width="100%"><tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the three months ended March 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</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_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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=122041274&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_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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=120381028&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=122041274&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_ResearchDevelopmentAndPatentExpensesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ResearchDevelopmentAndPatentExpensesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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=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=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_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_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_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_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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_ExecutiveOfficerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ExecutiveOfficerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheThreeMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ShareBasedCompensationAwardTrancheThreeMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>42
<FILENAME>R32.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624040600472">
<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, 2022</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">63.00%<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">30.00%<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">7.00%<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">93.00%<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>
</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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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_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>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>43
<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">
							function toggleNextSibling (e) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624034369112">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Investments, Summary of Investments (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2022 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_InvestmentsAllOtherInvestmentsAbstract', window );"><strong>Ownership Interests in Private and Public Companies [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of private companies in which there is an equity ownership interest of less than 20% | Company</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of public companies in which there is an equity ownership interest of less than 20% | Company</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="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_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,602,517<span></span>
</td>
<td class="nump">$ 1,278,684<span></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_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">20,880<span></span>
</td>
<td class="nump">25,115<span></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_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(23,308)<span></span>
</td>
<td class="num">(5,148)<span></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_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,600,089<span></span>
</td>
<td class="nump">1,298,651<span></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_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets', window );">Number of publicly traded companies in which there is an investment included in other current assets | Company</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_BicycleTherapeuticsPlcMember', window );">Bicycle [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 custom" 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">$ (3,200)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_ProqrTherapeuticsNVMember', window );">ProQR [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="re">
<td class="pl custom" 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">(3,400)<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_FinancialInstrumentAxis=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,567,505<span></span>
</td>
<td class="nump">1,251,172<span></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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">227<span></span>
</td>
<td class="nump">1,263<span></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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(19,034)<span></span>
</td>
<td class="num">(4,311)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,548,698<span></span>
</td>
<td class="nump">1,248,124<span></span>
</td>
</tr>
<tr class="rh">
<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=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">949,813<span></span>
</td>
<td class="nump">612,557<span></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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">133<span></span>
</td>
<td class="nump">792<span></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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(3,423)<span></span>
</td>
<td class="num">(345)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">946,523<span></span>
</td>
<td class="nump">613,004<span></span>
</td>
</tr>
<tr class="rh">
<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=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">617,692<span></span>
</td>
<td class="nump">638,615<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">94<span></span>
</td>
<td class="nump">471<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(15,611)<span></span>
</td>
<td class="num">(3,966)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">602,175<span></span>
</td>
<td class="nump">635,120<span></span>
</td>
</tr>
<tr class="rh">
<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=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">420,081<span></span>
</td>
<td class="nump">383,870<span></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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">131<span></span>
</td>
<td class="nump">728<span></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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,766)<span></span>
</td>
<td class="num">(226)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">418,446<span></span>
</td>
<td class="nump">384,372<span></span>
</td>
</tr>
<tr class="rh">
<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=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">345,813<span></span>
</td>
<td class="nump">382,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">24<span></span>
</td>
<td class="nump">331<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(10,275)<span></span>
</td>
<td class="num">(2,644)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">335,562<span></span>
</td>
<td class="nump">379,687<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">34,407<span></span>
</td>
<td class="nump">48,493<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">19<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(49)<span></span>
</td>
<td class="num">(18)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">34,358<span></span>
</td>
<td class="nump">48,494<span></span>
</td>
</tr>
<tr class="rh">
<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=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">72,844<span></span>
</td>
<td class="nump">72,935<span></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_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 custom" 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">(1,974)<span></span>
</td>
<td class="num">(561)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">70,870<span></span>
</td>
<td class="nump">72,374<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">330,358<span></span>
</td>
<td class="nump">45,424<span></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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,133)<span></span>
</td>
<td class="num">(64)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">329,226<span></span>
</td>
<td class="nump">45,360<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_FinancialInstrumentAxis=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">164,040<span></span>
</td>
<td class="nump">137,635<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">70<span></span>
</td>
<td class="nump">139<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(2,544)<span></span>
</td>
<td class="num">(500)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">161,566<span></span>
</td>
<td class="nump">137,274<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member] | 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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">158,548<span></span>
</td>
<td class="nump">134,770<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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<span></span>
</td>
<td class="nump">45<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(376)<span></span>
</td>
<td class="num">(37)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">158,173<span></span>
</td>
<td class="nump">134,778<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_us-gaap_FinancialInstrumentAxis=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">34,995<span></span>
</td>
<td class="nump">39,909<span></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_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">1<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(818)<span></span>
</td>
<td class="num">(224)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">34,177<span></span>
</td>
<td class="nump">39,686<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6,419<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(99)<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6,320<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,136<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="text">&#160;<span></span>
</td>
<td class="num">(37)<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,099<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">35,012<span></span>
</td>
<td class="nump">27,512<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">20,653<span></span>
</td>
<td class="nump">23,852<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(4,274)<span></span>
</td>
<td class="num">(837)<span></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_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">51,391<span></span>
</td>
<td class="nump">50,527<span></span>
</td>
</tr>
<tr class="rh">
<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_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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">11,897<span></span>
</td>
<td class="nump">11,897<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">3,946<span></span>
</td>
<td class="nump">7,145<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">(4,274)<span></span>
</td>
<td class="num">(837)<span></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_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">11,569<span></span>
</td>
<td class="nump">18,205<span></span>
</td>
</tr>
<tr class="rh">
<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_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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">23,115<span></span>
</td>
<td class="nump">15,615<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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">16,707<span></span>
</td>
<td class="nump">16,707<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" 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">$ 39,822<span></span>
</td>
<td class="nump">$ 32,322<span></span>
</td>
</tr>
<tr><td colspan="3"></td></tr>
<tr><td colspan="3"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Includes investments classified as cash equivalents 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">Our equity securities included in other current assets consisted of our investments in two publicly traded companies, ProQR and Bicycle, which we classify as Level 1 and Level 3 investments, respectively. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2022, we recognized a $3.4 million and a $3.2 million unrealized loss on our condensed consolidated statement of operations related to our investments in ProQR and Bicycle, respectively. In the three months ended March 31, 2021, our equity securities included in other current assets only consisted of ProQR.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total of (1) investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total of (1) amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total of (1) unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Total of (1) unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_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_ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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-traded companies in which the entity has an equity investment included in other current assets.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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=123581744&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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=123581744&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123581744&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=124258926&amp;loc=SL82898722-210454<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26610-111562<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -URI http://asc.fasb.org/extlink&amp;oid=123581744&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), 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 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=123594786&amp;loc=SL75136599-209740<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNiCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI). Excludes equity method investment and investment in equity security without readily determinable fair value.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNiCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNiUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=123583765&amp;loc=SL75117546-209714<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNiUnrealizedGain</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=123583765&amp;loc=SL75117546-209714<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNiUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_BicycleTherapeuticsPlcMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_BicycleTherapeuticsPlcMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_ProqrTherapeuticsNVMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_ProqrTherapeuticsNVMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_DebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_DebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfOneYearOrLessMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfOneYearOrLessMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfMoreThanOneYearMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentSecondaryCategorizationAxis=ions_SecuritiesWithMaturityOfMoreThanOneYearMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_USTreasurySecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_OtherDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_EquitySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_EquitySecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_EquitySecuritiesPubliclyTradedCompaniesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPrivateCompaniesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_EquitySecuritiesPrivateCompaniesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>44
<FILENAME>R34.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624036329064">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Investments, Investments Temporarily Impaired (Details)<br> $ in Thousands</strong></div></th>
<th class="th">
<div>Mar. 31, 2022 </div>
<div>USD ($) </div>
<div>Investment</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">1,017<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 1,324,532<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">36,305<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">1,360,837<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(18,042)<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(992)<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (19,034)<span></span>
</td>
</tr>
<tr class="rh">
<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=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">337<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 647,390<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">11,300<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">658,690<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(11,694)<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(347)<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (12,041)<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_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">14<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 95,543<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">9,685<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">105,228<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(1,697)<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(326)<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (2,023)<span></span>
</td>
</tr>
<tr class="rh">
<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=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">44<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 406,747<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">4,860<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">411,607<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(3,539)<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(138)<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (3,677)<span></span>
</td>
</tr>
<tr class="rh">
<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=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">619<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 173,537<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">5,455<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">178,992<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(1,096)<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(98)<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (1,194)<span></span>
</td>
</tr>
<tr class="rh">
<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=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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', 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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 1,315<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">5,005<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">6,320<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(16)<span></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_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(83)<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_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (99)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_AvailableForSaleSecuritiesAbstract</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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), in continuous unrealized loss position for more than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="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 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=123581744&amp;loc=d3e27337-111563<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=121590138&amp;loc=SL82922954-210456<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for 12 months or longer, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="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 7<br> -URI http://asc.fasb.org/extlink&amp;oid=123581744&amp;loc=d3e27337-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="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 7<br> -URI http://asc.fasb.org/extlink&amp;oid=123581744&amp;loc=d3e27337-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=121590138&amp;loc=SL82922954-210456<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="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 50<br> -Paragraph 5<br> -URI http://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI http://asc.fasb.org/extlink&amp;oid=123581744&amp;loc=d3e27337-111563<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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 debt securities measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without an allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="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 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(3)<br> -URI http://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922888-210455<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</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_DebtSecuritiesAvailableForSaleUnrealizedLossPosition">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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), in unrealized loss position without allowance for credit loss.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=123581744&amp;loc=d3e27290-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)(1)<br> -URI http://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922888-210455<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=121590138&amp;loc=SL82922954-210456<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in unrealized loss position, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="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 6<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=123581744&amp;loc=d3e27290-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922888-210455<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_CorporateDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_USTreasurySecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_OtherDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>45
<FILENAME>R35.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624033460952">
<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, 2022</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Mar. 31, 2021</div></th>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<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% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 494,400<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">595,400<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">407,399<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 541,199<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</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_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,967,666<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,807,528<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Bicycle Therapeutics plc [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_EquitySecuritiesFvNi', window );">Investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">11,131<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">14,330<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | ProQR Therapeutics N.V. [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_EquitySecuritiesFvNi', window );">Investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">438<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">3,875<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">754,008<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">764,059<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">13,500<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">105,228<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">120,868<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Cash and Cash Equivalents [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,300<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">490,792<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="nump">182,634<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">15,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">192,350<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[6]</sup></td>
<td class="nump">174,464<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[7]</sup></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Cash and Cash Equivalents [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">10,300<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">6,320<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,099<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">407,399<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">541,199<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</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_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">898,629<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">727,708<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Bicycle Therapeutics plc [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_EquitySecuritiesFvNi', window );">Investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | ProQR Therapeutics N.V. [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_EquitySecuritiesFvNi', window );">Investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">438<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">3,875<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">490,792<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">182,634<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</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_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,057,906<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,065,490<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Bicycle Therapeutics plc [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_EquitySecuritiesFvNi', window );">Investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | ProQR Therapeutics N.V. [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_EquitySecuritiesFvNi', window );">Investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">754,008<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">764,059<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">105,228<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">120,868<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">192,350<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">174,464<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6,320<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,099<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</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_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">11,131<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">14,330<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Bicycle Therapeutics plc [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_EquitySecuritiesFvNi', window );">Investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">11,131<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">14,330<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | ProQR Therapeutics N.V. [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_EquitySecuritiesFvNi', window );">Investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></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_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="6"></td></tr>
<tr><td colspan="6"><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">$13.5 million was 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>
<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">$15.0 million was 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>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[6]</td>
<td style="vertical-align: top;" valign="top">$10.3 million was 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>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[7]</td>
<td style="vertical-align: top;" valign="top">$2.3 million was 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;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AssetsFairValueDisclosure">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123874694&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_AssetsFairValueDisclosure</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -URI http://asc.fasb.org/extlink&amp;oid=120398452&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26610-111562<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -URI http://asc.fasb.org/extlink&amp;oid=123581744&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of currency on hand as well as demand deposits with banks or financial institutions. Includes other kinds of accounts that have the general characteristics of demand deposits. Also includes short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashAndCashEquivalentsFairValueDisclosure</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI 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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), 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 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI http://asc.fasb.org/extlink&amp;oid=123594786&amp;loc=SL75136599-209740<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FairValueNetAssetLiabilityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_FairValueNetAssetLiabilityAbstract</td>
</tr>
<tr>
<td style="padding-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_NotesPayableFairValueDisclosure">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of 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>
<td style="white-space:nowrap;">us-gaap_NotesPayableFairValueDisclosure</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance 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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel2Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_BicycleTherapeuticsPlcMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_BicycleTherapeuticsPlcMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_ProqrTherapeuticsNVMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis=ions_ProqrTherapeuticsNVMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_BalanceSheetLocationAxis=us-gaap_CashAndCashEquivalentsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_BalanceSheetLocationAxis=us-gaap_CashAndCashEquivalentsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_USTreasurySecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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=us-gaap_OtherDebtSecuritiesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel1Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel1Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel3Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel3Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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>46
<FILENAME>R36.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624120732840">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2022</div></th>
<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_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [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_AmortizationPeriodForResearchAndDevelopmentExpenditures', window );">Amortization period for research and development expenditures under IRC Section 174</a></td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax expense</a></td>
<td class="nump">$ 1,094<span></span>
</td>
<td class="nump">$ 130<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AmortizationPeriodForResearchAndDevelopmentExpenditures">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Amortization period for research and development expenditures under Internal Revenue Code Section 174, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AmortizationPeriodForResearchAndDevelopmentExpenditures</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI http://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI http://asc.fasb.org/extlink&amp;oid=123359005&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=124431687&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123586238&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI 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=124431687&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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>47
<FILENAME>R37.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) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624033961400">
<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="3">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2022 </div>
<div>USD ($) </div>
<div>Target</div>
</th>
<th class="th">
<div>Jun. 30, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 141,919<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>
</tr>
<tr 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 custom" 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">53,818<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">59,986<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_ResearchAndDevelopmentRevenueMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">69,634<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">27,159<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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_BiogenCollaborationsMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">3,300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">93,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 78,100<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 385,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 407,500<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">66.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70.00%<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_BiogenCollaborationsMember', window );">Biogen [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 53,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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_BiogenCollaborationsMember', window );">Biogen [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">40,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 18,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></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="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_NumberOfTargetsAdvanced', window );">Number of targets advanced | Target</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member] | ION541 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr 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_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></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>
</tr>
<tr class="rh">
<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_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl " style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_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">$ 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_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_NumberOfTargetsAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 targets advanced under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTargetsAdvanced</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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=123359005&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=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI 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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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=123360276&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=123351226&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=123360276&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=123359005&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=123359005&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=123359005&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=123359005&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=123359005&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=123351226&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=123359005&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=123359005&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=123359005&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=123351226&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_ResearchAndDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_ResearchAndDevelopmentRevenueMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_BiogenCollaborationsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_BiogenCollaboration2013StrategicNeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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_BiogenCollaboration2013StrategicNeurologyMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_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_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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>48
<FILENAME>R38.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
							function toggleNextSibling (e) {
							if (e.nextSibling.style.display=='none') {
							e.nextSibling.style.display='block';
							} else { e.nextSibling.style.display='none'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.22.1</span><table class="report" border="0" cellspacing="2" id="idm139624035784968">
<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="3">1 Months Ended</th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Nov. 30, 2021</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Mar. 31, 2022</div></th>
<th class="th"><div>Jun. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<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_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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">$ 46.9<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136.7<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">89.8<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="text">&#160;<span></span>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 632.5<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 custom" 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="text">&#160;<span></span>
</td>
<td class="nump">$ 12.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Apr. 30,  2026<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" 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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 57.84<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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="text">&#160;<span></span>
</td>
<td class="nump">$ 76.39<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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="text">&#160;<span></span>
</td>
<td class="nump">10.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 548.8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="top.Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 6.0<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_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Dec. 31,  2024<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<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_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 83.28<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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="text">&#160;<span></span>
</td>
<td class="nump">$ 123.38<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="nump">6.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<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% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">247.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible notes</a></td>
<td class="nump">$ 62.0<span></span>
</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</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_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="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="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></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=123466204&amp;loc=SL6031897-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(16))<br> -URI 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=123466204&amp;loc=SL6031898-161870<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (c)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentConvertibleConversionPrice1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28551-108399<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI http://asc.fasb.org/extlink&amp;oid=114775985&amp;loc=d3e28878-108400<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=124429444&amp;loc=SL124452920-239629<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69C<br> -URI http://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495737-112612<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69B<br> -URI http://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495735-112612<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentFaceAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Effective interest rate for the funds borrowed under the debt agreement considering interest compounding and original issue discount or premium.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466204&amp;loc=SL6036836-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28551-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI http://asc.fasb.org/extlink&amp;oid=124429444&amp;loc=SL124452920-239629<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI 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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI 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>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentMaturityDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></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 YYYY-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/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (d)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -URI http://asc.fasb.org/extlink&amp;oid=123874694&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://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (a)<br> -URI http://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495340-112611<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI http://asc.fasb.org/extlink&amp;oid=124435984&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_GainsLossesOnExtinguishmentOfDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Definition</a><div><p>Difference between the fair value of payments made and the carrying amount of debt which is extinguished prior to maturity.</p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -URI http://asc.fasb.org/extlink&amp;oid=123467658&amp;loc=d3e12355-112629<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -URI http://asc.fasb.org/extlink&amp;oid=123467658&amp;loc=d3e12317-112629<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI http://asc.fasb.org/extlink&amp;oid=123570139&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainsLossesOnExtinguishmentOfDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_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=123570139&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=123570139&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=123570139&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=123570139&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_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>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="top.Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="top.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>
</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>49
<FILENAME>form10q_htm.xml
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<XML>
<?xml version="1.0" encoding="utf-8"?>
<xbrl
  xmlns="http://www.xbrl.org/2003/instance"
  xmlns:dei="http://xbrl.sec.gov/dei/2021q4"
  xmlns:ions="http://ionispharma.com/20220331"
  xmlns:iso4217="http://www.xbrl.org/2003/iso4217"
  xmlns:link="http://www.xbrl.org/2003/linkbase"
  xmlns:srt="http://fasb.org/srt/2021-01-31"
  xmlns:us-gaap="http://fasb.org/us-gaap/2021-01-31"
  xmlns:xbrldi="http://xbrl.org/2006/xbrldi"
  xmlns:xhtml="http://www.w3.org/1999/xhtml"
  xmlns:xlink="http://www.w3.org/1999/xlink">
    <link:schemaRef xlink:href="ions-20220331.xsd" xlink:type="simple"/>
    <context id="c20220101to20220331">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220428">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2022-04-28</instant>
        </period>
    </context>
    <context id="c20220331">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CollaborativeAgreementRevenueMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CollaborativeAgreementRevenueMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_SpinrazaRoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SpinrazaRoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:EplontersenJointDevelopmentRevenueMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:LicensingAndOtherRoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ProductOrServiceAxis_SpinrazaRoyaltiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SpinrazaRoyaltiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:EplontersenJointDevelopmentRevenueMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_ProductMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ProductOrServiceAxis_ProductMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">us-gaap:ProductMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_CommercialMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ProductOrServiceAxis_CommercialMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:CommercialMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20201231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2020-12-31</instant>
        </period>
    </context>
    <context id="c20201231_StatementEquityComponentsAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2020-12-31</instant>
        </period>
    </context>
    <context id="c20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20201231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2020-12-31</instant>
        </period>
    </context>
    <context id="c20211231_StatementEquityComponentsAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_StatementEquityComponentsAxis_RetainedEarningsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20201231_StatementEquityComponentsAxis_RetainedEarningsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2020-12-31</instant>
        </period>
    </context>
    <context id="c20201231">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2020-12-31</instant>
        </period>
    </context>
    <context id="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220331_StatementEquityComponentsAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_StatementEquityComponentsAxis_RetainedEarningsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20210331_StatementEquityComponentsAxis_RetainedEarningsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:RetainedEarningsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-03-31</instant>
        </period>
    </context>
    <context id="c20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20210331">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <instant>2021-03-31</instant>
        </period>
    </context>
    <context id="c20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-03-31</instant>
        </period>
    </context>
    <context id="c20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AccumulatedOtherComprehensiveIncomeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-03-31</instant>
        </period>
    </context>
    <context id="c20210331_StatementEquityComponentsAxis_CommonStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:CommonStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-03-31</instant>
        </period>
    </context>
    <context id="c20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:StatementEquityComponentsAxis">us-gaap:AdditionalPaidInCapitalMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20211001to20211231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:Ion306Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-10-01</startDate>
            <endDate>2021-12-31</endDate>
        </period>
    </context>
    <context id="c20210101to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:AstrazenecaCollaborationEplontersenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-12-31</endDate>
        </period>
    </context>
    <context id="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:AlnylamCollaborationMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2020-10-01</startDate>
            <endDate>2020-12-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_Ion859Member">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:Ion859Member</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaboration2013StrategicNeurologyMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20181001to20181231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:RocheCollaborationIonisFbLForComplementMediatedDiseasesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-10-01</startDate>
            <endDate>2018-12-31</endDate>
        </period>
    </context>
    <context id="c20211001to20211231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaboration2018StrategicNeurologyMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-10-01</startDate>
            <endDate>2021-12-31</endDate>
        </period>
    </context>
    <context id="c20180401to20180630_MajorCustomersAxis_BiogenIncMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:MajorCustomersAxis">ions:BiogenIncMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2018-04-01</startDate>
            <endDate>2018-06-30</endDate>
        </period>
    </context>
    <context id="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:AstrazenecaCollaborationEplontersenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220101to20220331_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:AstrazenecaCollaborationEplontersenMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:MajorCustomersAxis">ions:TwoSignificantCustomersMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:AccountsReceivableMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CreditConcentrationRiskMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-12-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:MajorCustomersAxis">ions:TwoSignificantCustomersMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:AccountsReceivableMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CreditConcentrationRiskMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20211231">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-12-31</endDate>
        </period>
    </context>
    <context id="c20200101to20201231">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2020-01-01</startDate>
            <endDate>2020-12-31</endDate>
        </period>
    </context>
    <context id="c20200101to20201231_FinancialInstrumentAxis_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2020-01-01</startDate>
            <endDate>2020-12-31</endDate>
        </period>
    </context>
    <context id="c20211231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PublicUtilitiesInventoryAxis">ions:CommercialRawMaterialsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PublicUtilitiesInventoryAxis">ions:ClinicalRawMaterialsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PublicUtilitiesInventoryAxis">ions:CommercialRawMaterialsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PublicUtilitiesInventoryAxis">ions:ClinicalRawMaterialsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220101to20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">us-gaap:BuildingMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:PropertyPlantAndEquipmentByTypeAxis">us-gaap:BuildingMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-03-31</instant>
        </period>
    </context>
    <context id="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-03-31</instant>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">us-gaap:ShareBasedPaymentArrangementEmployeeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">us-gaap:ShareBasedPaymentArrangementEmployeeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_EmployeeStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_AwardTypeAxis_EmployeeStockMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">ions:ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheThreeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:VestingAxis">us-gaap:ShareBasedCompensationAwardTrancheThreeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheOneMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:VestingAxis">us-gaap:ShareBasedCompensationAwardTrancheOneMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheTwoMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:VestingAxis">us-gaap:ShareBasedCompensationAwardTrancheTwoMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MinimumMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:RangeAxis">srt:MinimumMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">ions:ShareBasedPaymentArrangementBoardOfDirectorMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MaximumMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:RangeAxis">srt:MaximumMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">ions:ShareBasedPaymentArrangementBoardOfDirectorMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">us-gaap:ShareBasedPaymentArrangementEmployeeMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:RangeAxis">srt:MaximumMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:RangeAxis">srt:MinimumMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:GranteeStatusAxis">srt:ExecutiveOfficerMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220331_AwardTypeAxis_EmployeeStockOptionMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_AwardTypeAxis_PerformanceSharesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:PerformanceSharesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:RestrictedStockUnitsRSUMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:AwardTypeAxis">us-gaap:EmployeeStockOptionMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentExpensesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">us-gaap:SellingGeneralAndAdministrativeExpensesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_IncomeStatementLocationAxis_CostOfSalesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">us-gaap:CostOfSalesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">us-gaap:SellingGeneralAndAdministrativeExpensesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">ions:ResearchDevelopmentAndPatentExpensesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_IncomeStatementLocationAxis_CostOfSalesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:IncomeStatementLocationAxis">us-gaap:CostOfSalesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfMoreThanOneYearMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:DebtSecuritiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:InvestmentSecondaryCategorizationAxis">ions:SecuritiesWithMaturityOfOneYearOrLessMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_EquitySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:EquitySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPrivateCompaniesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPubliclyTradedCompaniesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPubliclyTradedCompaniesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_EquitySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:EquitySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPrivateCompaniesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPrivateCompaniesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPrivateCompaniesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-12-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPubliclyTradedCompaniesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">ions:EquitySecuritiesPubliclyTradedCompaniesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-12-31</endDate>
        </period>
    </context>
    <context id="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:EquitySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-12-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:EquitySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:CorporateDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:OtherDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USGovernmentAgenciesDebtSecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:BalanceSheetLocationAxis">us-gaap:CashAndCashEquivalentsMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USStatesAndPoliticalSubdivisionsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FinancialInstrumentAxis">us-gaap:USTreasurySecuritiesMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:ProqrTherapeuticsNVMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel3Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel1Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis">ions:BicycleTherapeuticsPlcMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByMeasurementFrequencyAxis">us-gaap:FairValueMeasurementsRecurringMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0125PercentMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:FairValueByFairValueHierarchyLevelAxis">us-gaap:FairValueInputsLevel2Member</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20220331_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20210401to20210630_ProductOrServiceAxis_Ion541Member_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:Ion541Member</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaboration2013StrategicNeurologyMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-04-01</startDate>
            <endDate>2021-06-30</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ProductOrServiceAxis_SpinrazaRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SpinrazaRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:ResearchAndDevelopmentRevenueMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ProductOrServiceAxis_SpinrazaRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:ProductOrServiceAxis">ions:SpinrazaRoyaltiesMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20210101to20210331_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:RevenueFromContractWithCustomerMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-01-01</startDate>
            <endDate>2021-03-31</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByBenchmarkAxis">us-gaap:RevenueFromContractWithCustomerMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:ConcentrationRiskByTypeAxis">us-gaap:CustomerConcentrationRiskMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <context id="c20211231_TypeOfArrangementAxis_BiogenCollaborationsMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaborationsMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-12-31</instant>
        </period>
    </context>
    <context id="c20220331_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="srt:RangeAxis">srt:MaximumMember</xbrldi:explicitMember>
                <xbrldi:explicitMember dimension="us-gaap:TypeOfArrangementAxis">ions:BiogenCollaboration2013StrategicNeurologyMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes0PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-04-30</instant>
        </period>
    </context>
    <context id="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2021-04-30</instant>
        </period>
    </context>
    <context id="c20211101to20211130_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-11-01</startDate>
            <endDate>2021-11-30</endDate>
        </period>
    </context>
    <context id="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-04-01</startDate>
            <endDate>2021-04-30</endDate>
        </period>
    </context>
    <context id="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <instant>2022-03-31</instant>
        </period>
    </context>
    <context id="c20210401to20210430">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2021-04-01</startDate>
            <endDate>2021-04-30</endDate>
        </period>
    </context>
    <context id="c20191201to20191231">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
        </entity>
        <period>
            <startDate>2019-12-01</startDate>
            <endDate>2019-12-31</endDate>
        </period>
    </context>
    <context id="c20210401to20210630_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2021-04-01</startDate>
            <endDate>2021-06-30</endDate>
        </period>
    </context>
    <context id="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember">
        <entity>
            <identifier scheme="http://www.sec.gov/CIK">0000874015</identifier>
            <segment>
                <xbrldi:explicitMember dimension="us-gaap:DebtInstrumentAxis">ions:ConvertibleSeniorNotes1PercentMember</xbrldi:explicitMember>
            </segment>
        </entity>
        <period>
            <startDate>2022-01-01</startDate>
            <endDate>2022-03-31</endDate>
        </period>
    </context>
    <unit id="U001">
        <measure>shares</measure>
    </unit>
    <unit id="U002">
        <measure>iso4217:USD</measure>
    </unit>
    <unit id="U003">
        <measure>pure</measure>
    </unit>
    <unit id="U004">
        <divide>
            <unitNumerator>
                <measure>iso4217:USD</measure>
            </unitNumerator>
            <unitDenominator>
                <measure>shares</measure>
            </unitDenominator>
        </divide>
    </unit>
    <unit id="U005">
        <measure>ions:Target</measure>
    </unit>
    <unit id="U006">
        <measure>ions:Agreement</measure>
    </unit>
    <unit id="U007">
        <measure>ions:Component</measure>
    </unit>
    <unit id="U008">
        <measure>ions:PerformanceObligation</measure>
    </unit>
    <unit id="U009">
        <measure>ions:Partner</measure>
    </unit>
    <unit id="U010">
        <measure>ions:Company</measure>
    </unit>
    <unit id="U011">
        <measure>ions:Investment</measure>
    </unit>
    <unit id="U012">
        <measure>ions:Segment</measure>
    </unit>
    <unit id="U013">
        <measure>ions:Period</measure>
    </unit>
    <dei:AmendmentFlag
      contextRef="c20220101to20220331"
      id="Fact_f0028d42fdf94d64b2e43d0c644f41ff">false</dei:AmendmentFlag>
    <dei:CurrentFiscalYearEndDate
      contextRef="c20220101to20220331"
      id="Fact_8e41f7c37386421e81c89573ae2e32fa">--12-31</dei:CurrentFiscalYearEndDate>
    <dei:DocumentFiscalYearFocus
      contextRef="c20220101to20220331"
      id="Fact_4ae580782bac4f62861c520f102b5a43">2022</dei:DocumentFiscalYearFocus>
    <dei:DocumentFiscalPeriodFocus
      contextRef="c20220101to20220331"
      id="Fact_307b3d7761e048a9a1981817f8746bff">Q1</dei:DocumentFiscalPeriodFocus>
    <dei:EntityCentralIndexKey
      contextRef="c20220101to20220331"
      id="Fact_5b9de3963cb8400e85b7297a1c736a9e">0000874015</dei:EntityCentralIndexKey>
    <ions:PeriodAfterBillingWhenPaymentIsReceived
      contextRef="c20220101to20220331"
      id="Fact_cb46feec840d4d05b86df2a2af3b44c3">P3M</ions:PeriodAfterBillingWhenPaymentIsReceived>
    <us-gaap:NumberOfOperatingSegments
      contextRef="c20220101to20220331"
      decimals="INF"
      id="Fact_ba6a4e8bb35940dbbf919d263b57d70e"
      unitRef="U012">1</us-gaap:NumberOfOperatingSegments>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheThreeMember"
      decimals="3"
      id="Fact_3ea144f70898401099a1731ad0c7e39f"
      unitRef="U003">0.333</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheOneMember"
      decimals="3"
      id="Fact_b2b6dbe875764e78b9cce0b8464216dd"
      unitRef="U003">0.333</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheTwoMember"
      decimals="3"
      id="Fact_b531c97d5a394e3f8a5454ecd82ddb93"
      unitRef="U003">0.333</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage>
    <ions:MaximumContractMaturityPeriodRange3
      contextRef="c20220101to20220331"
      id="Fact_f12cc57cfa544d218ac6c26f9aae5797">P3Y6M</ions:MaximumContractMaturityPeriodRange3>
    <us-gaap:DebtInstrumentMaturityDate
      contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      id="Fact_109f9369bddf4793b7c1ba8f66869fde">2026-04-30</us-gaap:DebtInstrumentMaturityDate>
    <us-gaap:DebtInstrumentMaturityDate
      contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      id="Fact_c5b254d960d242d380e7e1f35dc8b7ec">2024-12-31</us-gaap:DebtInstrumentMaturityDate>
    <dei:DocumentType
      contextRef="c20220101to20220331"
      id="Fact_28d55d59b48a47e298c5f1f8acda983a">10-Q</dei:DocumentType>
    <dei:DocumentQuarterlyReport
      contextRef="c20220101to20220331"
      id="Fact_5bbd70fef0434e0bb3005d7ef54a8498">true</dei:DocumentQuarterlyReport>
    <dei:DocumentPeriodEndDate
      contextRef="c20220101to20220331"
      id="Fact_6e9df661fd6a49358b0d67aa84c8eb02">2022-03-31</dei:DocumentPeriodEndDate>
    <dei:DocumentTransitionReport
      contextRef="c20220101to20220331"
      id="Fact_22e4da1d333a4f3ca9ed4cd00d7bb801">false</dei:DocumentTransitionReport>
    <dei:EntityFileNumber
      contextRef="c20220101to20220331"
      id="Fact_69eb5d1f30814d11a7d3f1427421815b">000-19125</dei:EntityFileNumber>
    <dei:EntityRegistrantName
      contextRef="c20220101to20220331"
      id="Fact_423ffc6a28b44260828511a52e661ffa">Ionis Pharmaceuticals, Inc.</dei:EntityRegistrantName>
    <dei:EntityIncorporationStateCountryCode
      contextRef="c20220101to20220331"
      id="Fact_5e56b955d0c64e368cbede0122260b2c">DE</dei:EntityIncorporationStateCountryCode>
    <dei:EntityTaxIdentificationNumber
      contextRef="c20220101to20220331"
      id="Fact_2112da11bf8747ad9520c7538638757b">33-0336973</dei:EntityTaxIdentificationNumber>
    <dei:EntityAddressAddressLine1
      contextRef="c20220101to20220331"
      id="Fact_3a6566c78c6c48838724649b631cc6ac">2855 Gazelle Court</dei:EntityAddressAddressLine1>
    <dei:EntityAddressCityOrTown
      contextRef="c20220101to20220331"
      id="Fact_d65c210a405e49f0ba72838f7eac119f">Carlsbad</dei:EntityAddressCityOrTown>
    <dei:EntityAddressStateOrProvince
      contextRef="c20220101to20220331"
      id="Fact_8cd659ea51164b91987071f35e2fb911">CA</dei:EntityAddressStateOrProvince>
    <dei:EntityAddressPostalZipCode
      contextRef="c20220101to20220331"
      id="Fact_49278299ec2d46a5a610ccdb264e1ac9">92010</dei:EntityAddressPostalZipCode>
    <dei:CityAreaCode
      contextRef="c20220101to20220331"
      id="Fact_125734dd54044eaa89da14f2fc3d3bd0">760</dei:CityAreaCode>
    <dei:LocalPhoneNumber
      contextRef="c20220101to20220331"
      id="Fact_a35d14a198d2401d8934c4ba029a537f">931-9200</dei:LocalPhoneNumber>
    <dei:Security12bTitle
      contextRef="c20220101to20220331"
      id="Fact_52255b33c81f4d7cb25d3ed4925c361f">Common Stock, $.001 Par Value</dei:Security12bTitle>
    <dei:TradingSymbol
      contextRef="c20220101to20220331"
      id="Fact_e3a4cc74d20e45d8bff9336150b85ad0">IONS</dei:TradingSymbol>
    <dei:SecurityExchangeName
      contextRef="c20220101to20220331"
      id="Fact_8e4ded3e323748dc86453783a0f00869">NASDAQ</dei:SecurityExchangeName>
    <dei:EntityCurrentReportingStatus
      contextRef="c20220101to20220331"
      id="Fact_d3ee9e2530ea46e2b590e9f9cb002616">Yes</dei:EntityCurrentReportingStatus>
    <dei:EntityInteractiveDataCurrent
      contextRef="c20220101to20220331"
      id="Fact_191a54ad0b1c4c67aafb02582393d3d5">Yes</dei:EntityInteractiveDataCurrent>
    <dei:EntityFilerCategory
      contextRef="c20220101to20220331"
      id="Fact_25013b9234014ef296d27826b7cec20c">Large Accelerated Filer</dei:EntityFilerCategory>
    <dei:EntitySmallBusiness
      contextRef="c20220101to20220331"
      id="Fact_0f4d8a3583d64629b92e13dee079ecb1">false</dei:EntitySmallBusiness>
    <dei:EntityEmergingGrowthCompany
      contextRef="c20220101to20220331"
      id="Fact_b324ad6856c946fcb60ff103712caa84">false</dei:EntityEmergingGrowthCompany>
    <dei:EntityShellCompany
      contextRef="c20220101to20220331"
      id="Fact_3bc115f63d5d44be8cdbc2eba0d2aab7">false</dei:EntityShellCompany>
    <dei:EntityCommonStockSharesOutstanding
      contextRef="c20220428"
      decimals="INF"
      id="Fact_3a99a0f5d2b046e59520e673d7e403f7"
      unitRef="U001">141797854</dei:EntityCommonStockSharesOutstanding>
    <us-gaap:CashAndCashEquivalentsAtCarryingValue
      contextRef="c20220331"
      decimals="-3"
      id="Fact_58ab72fa50f24ffe98199f48fbe2c7f0"
      unitRef="U002">542513000</us-gaap:CashAndCashEquivalentsAtCarryingValue>
    <us-gaap:CashAndCashEquivalentsAtCarryingValue
      contextRef="c20211231"
      decimals="-3"
      id="Fact_a0cb8c640e1a44688ea7c7919293748f"
      unitRef="U002">869191000</us-gaap:CashAndCashEquivalentsAtCarryingValue>
    <us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_05d3c63942424d44b3a45d0e399d7509"
      unitRef="U002">1509880000</us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent>
    <us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_40b92a7d67634da98603b4b62a18fd2a"
      unitRef="U002">1245782000</us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent>
    <us-gaap:ContractWithCustomerAssetNetCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_42eb7b27d7ea459086945663ae763056"
      unitRef="U002">26122000</us-gaap:ContractWithCustomerAssetNetCurrent>
    <us-gaap:ContractWithCustomerAssetNetCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_90c87b1639e7454d862938e1695fb4ba"
      unitRef="U002">61896000</us-gaap:ContractWithCustomerAssetNetCurrent>
    <us-gaap:InventoryNet
      contextRef="c20220331"
      decimals="-3"
      id="Fact_bdc1851ec3a24426938e66ad4005713a"
      unitRef="U002">24032000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20211231"
      decimals="-3"
      id="Fact_efd195f3edec4c3091ff79a53462abb8"
      unitRef="U002">24806000</us-gaap:InventoryNet>
    <us-gaap:OtherAssetsCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_c0fa7bfa145e4eada7d79dd483724b5a"
      unitRef="U002">150577000</us-gaap:OtherAssetsCurrent>
    <us-gaap:OtherAssetsCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_a989f48740884b3f9c662b56d8ec6f22"
      unitRef="U002">143374000</us-gaap:OtherAssetsCurrent>
    <us-gaap:AssetsCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_4a277ae70920496a859de16b126a781a"
      unitRef="U002">2253124000</us-gaap:AssetsCurrent>
    <us-gaap:AssetsCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_e034b0a9b6284d72a53c220d22bd9ae4"
      unitRef="U002">2345049000</us-gaap:AssetsCurrent>
    <us-gaap:PropertyPlantAndEquipmentNet
      contextRef="c20220331"
      decimals="-3"
      id="Fact_4cf8028d82514177b93946aa1df7c264"
      unitRef="U002">177724000</us-gaap:PropertyPlantAndEquipmentNet>
    <us-gaap:PropertyPlantAndEquipmentNet
      contextRef="c20211231"
      decimals="-3"
      id="Fact_5ad23e93b4e4467b9feec47f0d291fee"
      unitRef="U002">178069000</us-gaap:PropertyPlantAndEquipmentNet>
    <us-gaap:FiniteLivedIntangibleAssetsNet
      contextRef="c20220331"
      decimals="-3"
      id="Fact_edce7eb26c0445978fe4ae3f9eed3d07"
      unitRef="U002">29295000</us-gaap:FiniteLivedIntangibleAssetsNet>
    <us-gaap:FiniteLivedIntangibleAssetsNet
      contextRef="c20211231"
      decimals="-3"
      id="Fact_7f0d3ff8c03f42ccb4e063d20c964f58"
      unitRef="U002">29005000</us-gaap:FiniteLivedIntangibleAssetsNet>
    <us-gaap:OtherAssetsNoncurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_d40d8e0c343c4faa8c8a1998eaa5093e"
      unitRef="U002">58949000</us-gaap:OtherAssetsNoncurrent>
    <us-gaap:OtherAssetsNoncurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_20e82d483df24cd682d948f6abcde7a0"
      unitRef="U002">59567000</us-gaap:OtherAssetsNoncurrent>
    <us-gaap:Assets
      contextRef="c20220331"
      decimals="-3"
      id="Fact_e57f61237ed14bad8578d2b47564ba8a"
      unitRef="U002">2519092000</us-gaap:Assets>
    <us-gaap:Assets
      contextRef="c20211231"
      decimals="-3"
      id="Fact_bacec939ac84418cbf35df017212761d"
      unitRef="U002">2611690000</us-gaap:Assets>
    <us-gaap:AccountsPayableCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_e36e66d0552f404099023f535d194dfe"
      unitRef="U002">16125000</us-gaap:AccountsPayableCurrent>
    <us-gaap:AccountsPayableCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_0c0b6424e746450abd937b9f839aed88"
      unitRef="U002">11904000</us-gaap:AccountsPayableCurrent>
    <us-gaap:EmployeeRelatedLiabilitiesCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_552968f4f2a9496e83f175a2ee89b95c"
      unitRef="U002">16525000</us-gaap:EmployeeRelatedLiabilitiesCurrent>
    <us-gaap:EmployeeRelatedLiabilitiesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_e06d0b21026d4d1db2ff5f69431f6629"
      unitRef="U002">38810000</us-gaap:EmployeeRelatedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_2fefcdea93734fcd9274bd7403d639f5"
      unitRef="U002">99256000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_213f5a6701c24aa0979bad8e60ab97c3"
      unitRef="U002">88560000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:AccruedIncomeTaxesCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_2af0ce9cd98b44bd81fc94205bb5c219"
      unitRef="U002">901000</us-gaap:AccruedIncomeTaxesCurrent>
    <us-gaap:AccruedIncomeTaxesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_7acc385f5ade40c4a52676f52d77facb"
      unitRef="U002">36000</us-gaap:AccruedIncomeTaxesCurrent>
    <ions:LongTermObligationsExcludingConvertibleDebtCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_bfee8ed3f29a415ba60a766b5e0cc4b7"
      unitRef="U002">4206000</ions:LongTermObligationsExcludingConvertibleDebtCurrent>
    <ions:LongTermObligationsExcludingConvertibleDebtCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_41e0bc055640457ebe9012a9d8313b03"
      unitRef="U002">3526000</ions:LongTermObligationsExcludingConvertibleDebtCurrent>
    <us-gaap:ContractWithCustomerLiabilityCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_09d676ed2f6648e5b73076a656df1277"
      unitRef="U002">91437000</us-gaap:ContractWithCustomerLiabilityCurrent>
    <us-gaap:ContractWithCustomerLiabilityCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_0b483c68b6994735bd21436d4b811df6"
      unitRef="U002">97714000</us-gaap:ContractWithCustomerLiabilityCurrent>
    <us-gaap:LiabilitiesCurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_b563c92d4e8b4add87b63f57c52a0e82"
      unitRef="U002">228450000</us-gaap:LiabilitiesCurrent>
    <us-gaap:LiabilitiesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_d521a592d7c446a7b398adb17b375e32"
      unitRef="U002">240550000</us-gaap:LiabilitiesCurrent>
    <us-gaap:ContractWithCustomerLiabilityNoncurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_8aa6408241e44715ba99551864adcae8"
      unitRef="U002">333138000</us-gaap:ContractWithCustomerLiabilityNoncurrent>
    <us-gaap:ContractWithCustomerLiabilityNoncurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_ede8dfed22c34e9582c277c64ee5a671"
      unitRef="U002">351879000</us-gaap:ContractWithCustomerLiabilityNoncurrent>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_17a2fd610eef4cd7a40de4f517482a78"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_25be9d36b918409db46b807933199820"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:ConvertibleDebtNoncurrent
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="-3"
      id="Fact_a398a9b03d9944b0a160b5b317b0ca9e"
      unitRef="U002">619898000</us-gaap:ConvertibleDebtNoncurrent>
    <us-gaap:ConvertibleDebtNoncurrent
      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="-3"
      id="Fact_6c57d7bc997a408eac5f0d23f91ceea6"
      unitRef="U002">619119000</us-gaap:ConvertibleDebtNoncurrent>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_65f01bf923dd44568923a6ad8fa6fbdd"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_4a872f1b79fe480980648870d88ebb8f"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:ConvertibleDebtNoncurrent
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-3"
      id="Fact_714a80b1e06f495582600aaf17011943"
      unitRef="U002">542860000</us-gaap:ConvertibleDebtNoncurrent>
    <us-gaap:ConvertibleDebtNoncurrent
      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-3"
      id="Fact_28e26d3aa3364b35803b96f04b984592"
      unitRef="U002">542314000</us-gaap:ConvertibleDebtNoncurrent>
    <ions:LongTermObligationsExcludingConvertibleDebtNoncurrent
      contextRef="c20220331"
      decimals="-3"
      id="Fact_fd5cf7d013b54a0388cfec028fd6a1c3"
      unitRef="U002">25710000</ions:LongTermObligationsExcludingConvertibleDebtNoncurrent>
    <ions:LongTermObligationsExcludingConvertibleDebtNoncurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_54d2771a1e14483ab99a8f4e34dd5224"
      unitRef="U002">26378000</ions:LongTermObligationsExcludingConvertibleDebtNoncurrent>
    <us-gaap:LongTermLoansFromBank
      contextRef="c20220331"
      decimals="-3"
      id="Fact_5af98209ca0a49319c15718880999db5"
      unitRef="U002">59462000</us-gaap:LongTermLoansFromBank>
    <us-gaap:LongTermLoansFromBank
      contextRef="c20211231"
      decimals="-3"
      id="Fact_b3ea6b13b4de4225adb6586558c16a06"
      unitRef="U002">59713000</us-gaap:LongTermLoansFromBank>
    <us-gaap:Liabilities
      contextRef="c20220331"
      decimals="-3"
      id="Fact_b675286a500340028e4203fe4698ca8a"
      unitRef="U002">1809518000</us-gaap:Liabilities>
    <us-gaap:Liabilities
      contextRef="c20211231"
      decimals="-3"
      id="Fact_f7cd0990ec2c4e71bcb30f7b03262cba"
      unitRef="U002">1839953000</us-gaap:Liabilities>
    <us-gaap:CommonStockParOrStatedValuePerShare
      contextRef="c20211231"
      decimals="3"
      id="Fact_89ceac2a6de84664a3444e0197c5952f"
      unitRef="U004">0.001</us-gaap:CommonStockParOrStatedValuePerShare>
    <us-gaap:CommonStockParOrStatedValuePerShare
      contextRef="c20220331"
      decimals="3"
      id="Fact_81d34c4177db42eb9566a4ebacfe9a61"
      unitRef="U004">0.001</us-gaap:CommonStockParOrStatedValuePerShare>
    <us-gaap:CommonStockSharesAuthorized
      contextRef="c20211231"
      decimals="0"
      id="Fact_c1d115fce5ca4643b306e1dda169e403"
      unitRef="U001">300000000</us-gaap:CommonStockSharesAuthorized>
    <us-gaap:CommonStockSharesAuthorized
      contextRef="c20220331"
      decimals="0"
      id="Fact_967e3bfa845149deb2a16ff5f6733824"
      unitRef="U001">300000000</us-gaap:CommonStockSharesAuthorized>
    <us-gaap:CommonStockSharesOutstanding
      contextRef="c20220331"
      decimals="0"
      id="Fact_7433a63c4a1045d2ab18a5f4dd2cfef3"
      unitRef="U001">141753122</us-gaap:CommonStockSharesOutstanding>
    <us-gaap:CommonStockSharesIssued
      contextRef="c20220331"
      decimals="0"
      id="Fact_aeabe9bc47984305a06e132d4d7bbbd3"
      unitRef="U001">141753122</us-gaap:CommonStockSharesIssued>
    <us-gaap:CommonStockSharesOutstanding
      contextRef="c20211231"
      decimals="0"
      id="Fact_16b1e67a7f564bfb8ebe67a950cecb91"
      unitRef="U001">141210015</us-gaap:CommonStockSharesOutstanding>
    <us-gaap:CommonStockSharesIssued
      contextRef="c20211231"
      decimals="0"
      id="Fact_987e70eb15fa4d6f8f4dee73a63054d5"
      unitRef="U001">141210015</us-gaap:CommonStockSharesIssued>
    <us-gaap:CommonStockValue
      contextRef="c20220331"
      decimals="-3"
      id="Fact_2ef68db29f344e1f9b9804fb82fc10d1"
      unitRef="U002">142000</us-gaap:CommonStockValue>
    <us-gaap:CommonStockValue
      contextRef="c20211231"
      decimals="-3"
      id="Fact_b57e377e7b024f69a86bf33102ea3c25"
      unitRef="U002">141000</us-gaap:CommonStockValue>
    <us-gaap:AdditionalPaidInCapitalCommonStock
      contextRef="c20220331"
      decimals="-3"
      id="Fact_aebda853ea1647d1b274290dee09ac0f"
      unitRef="U002">1983078000</us-gaap:AdditionalPaidInCapitalCommonStock>
    <us-gaap:AdditionalPaidInCapitalCommonStock
      contextRef="c20211231"
      decimals="-3"
      id="Fact_aee9cda9e03b48d4a74d89f28e31f6ec"
      unitRef="U002">1964167000</us-gaap:AdditionalPaidInCapitalCommonStock>
    <us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax
      contextRef="c20220331"
      decimals="-3"
      id="Fact_5df551453918447e8a86ae46f488bc1a"
      unitRef="U002">-48578000</us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax>
    <us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax
      contextRef="c20211231"
      decimals="-3"
      id="Fact_ce487df6de7f42f7b8c77a08d145dc67"
      unitRef="U002">-32668000</us-gaap:AccumulatedOtherComprehensiveIncomeLossNetOfTax>
    <us-gaap:RetainedEarningsAccumulatedDeficit
      contextRef="c20220331"
      decimals="-3"
      id="Fact_e5c1467d48e84e9db875c9a95c317d68"
      unitRef="U002">-1225068000</us-gaap:RetainedEarningsAccumulatedDeficit>
    <us-gaap:RetainedEarningsAccumulatedDeficit
      contextRef="c20211231"
      decimals="-3"
      id="Fact_49f9d5e423964e58bf47306bfe215fd4"
      unitRef="U002">-1159903000</us-gaap:RetainedEarningsAccumulatedDeficit>
    <us-gaap:StockholdersEquity
      contextRef="c20220331"
      decimals="-3"
      id="Fact_88e09c1d71dc4fa5bb36f4591af70f7e"
      unitRef="U002">709574000</us-gaap:StockholdersEquity>
    <us-gaap:StockholdersEquity
      contextRef="c20211231"
      decimals="-3"
      id="Fact_54e7a9222a6849019c33f1fa21e47093"
      unitRef="U002">771737000</us-gaap:StockholdersEquity>
    <us-gaap:LiabilitiesAndStockholdersEquity
      contextRef="c20220331"
      decimals="-3"
      id="Fact_1ff304ed0ed84581b2d4f5f331ecaa3f"
      unitRef="U002">2519092000</us-gaap:LiabilitiesAndStockholdersEquity>
    <us-gaap:LiabilitiesAndStockholdersEquity
      contextRef="c20211231"
      decimals="-3"
      id="Fact_8ae3d57392c94bea981bfe93b9c946c0"
      unitRef="U002">2611690000</us-gaap:LiabilitiesAndStockholdersEquity>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_SpinrazaRoyaltiesMember"
      decimals="-3"
      id="Fact_8ccc59285b1c4fde8c989da3abc6e321"
      unitRef="U002">53818000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_ProductOrServiceAxis_SpinrazaRoyaltiesMember"
      decimals="-3"
      id="Fact_e6ae93e981cd404c8ec41482c0c61a6a"
      unitRef="U002">59986000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_98f79b6da3a145ff8d1c7c7ea1a4ae6b"
      unitRef="U002">6160000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_ProductOrServiceAxis_ProductMember"
      decimals="-3"
      id="Fact_bd9d372310794274aada2c5b2070effc"
      unitRef="U002">19838000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_c20de44aa08a4feeb6ec553470e9e55b"
      unitRef="U002">12307000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_ProductOrServiceAxis_LicensingAndOtherRoyaltiesMember"
      decimals="-3"
      id="Fact_657d26ddec9a4b84ace6ae70602dd9e1"
      unitRef="U002">4624000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_bd6472880fbb416b95f903f2621fca89"
      unitRef="U002">72285000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_ProductOrServiceAxis_CommercialMember"
      decimals="-3"
      id="Fact_94547c1c92ad438eb4bebba69138f6b7"
      unitRef="U002">84448000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember"
      decimals="-3"
      id="Fact_a53a80c1d9e842e39354852481bc2e75"
      unitRef="U002">49784000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember"
      decimals="-3"
      id="Fact_bd7b5043e76a49b880159384c891417a"
      unitRef="U002">27159000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember"
      decimals="-3"
      id="Fact_26c235dd5e1c47a28eeb0d1c47f0907a"
      unitRef="U002">19850000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember"
      decimals="-3"
      id="Fact_a7adc01605f041fab7dcc375fff7caa0"
      unitRef="U002">0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember"
      decimals="-3"
      id="Fact_1f6c4e6ab7fd4eeba40d80f1b7c50537"
      unitRef="U002">69634000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember"
      decimals="-3"
      id="Fact_6baf09d075fa41ccb649de423a487613"
      unitRef="U002">27159000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_727ae23d59414052af7ab3decdd56184"
      unitRef="U002">141919000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_775c9b23f6344e2c8e38fc7161d48f97"
      unitRef="U002">111607000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:CostOfGoodsAndServicesSold
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_4149679d19a344ec8f07f14a2a4514d5"
      unitRef="U002">4170000</us-gaap:CostOfGoodsAndServicesSold>
    <us-gaap:CostOfGoodsAndServicesSold
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_68ba2fda58a44024be5ff63f94e807d0"
      unitRef="U002">2578000</us-gaap:CostOfGoodsAndServicesSold>
    <ions:ResearchDevelopmentAndPatentExpense
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_8fb85da59dd6434798e0931699f46727"
      unitRef="U002">161126000</ions:ResearchDevelopmentAndPatentExpense>
    <ions:ResearchDevelopmentAndPatentExpense
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_40cc4ce1957a47229dc8b59930865f9c"
      unitRef="U002">139801000</ions:ResearchDevelopmentAndPatentExpense>
    <us-gaap:SellingGeneralAndAdministrativeExpense
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_061c029e7dfc4b68ae21550ce885f82a"
      unitRef="U002">34127000</us-gaap:SellingGeneralAndAdministrativeExpense>
    <us-gaap:SellingGeneralAndAdministrativeExpense
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_7f9fe47be1834daca6afdaa55e9445df"
      unitRef="U002">61199000</us-gaap:SellingGeneralAndAdministrativeExpense>
    <us-gaap:CostsAndExpenses
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_7b9556ce8cc04ce5a47c736d803a80fb"
      unitRef="U002">199423000</us-gaap:CostsAndExpenses>
    <us-gaap:CostsAndExpenses
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_5ed3ac5e72714296ad9a3ea0d76f60ae"
      unitRef="U002">203578000</us-gaap:CostsAndExpenses>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_69031d54548341aabeedf33c8c504cfb"
      unitRef="U002">-57504000</us-gaap:OperatingIncomeLoss>
    <us-gaap:OperatingIncomeLoss
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_1c675860760d4b9bb6ea96cd58ebdacd"
      unitRef="U002">-91971000</us-gaap:OperatingIncomeLoss>
    <us-gaap:InvestmentIncomeNet
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_d67b485a811f4525906db85d0f12eab9"
      unitRef="U002">1993000</us-gaap:InvestmentIncomeNet>
    <us-gaap:InvestmentIncomeNet
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_c1b2d404bb1d44ff8372ae1e91a3906f"
      unitRef="U002">4643000</us-gaap:InvestmentIncomeNet>
    <us-gaap:InterestExpense
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_eace0ecd79fe4347aa41212bb38c8b40"
      unitRef="U002">2122000</us-gaap:InterestExpense>
    <us-gaap:InterestExpense
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_d2c45fb98baf4074b13f019638a4fbfb"
      unitRef="U002">2414000</us-gaap:InterestExpense>
    <us-gaap:GainLossOnInvestments
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_4f3cbaabe9b54db0adba894330e3dc9d"
      unitRef="U002">-6625000</us-gaap:GainLossOnInvestments>
    <us-gaap:GainLossOnInvestments
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_ed4f422854074183a8650e6e88000e26"
      unitRef="U002">0</us-gaap:GainLossOnInvestments>
    <us-gaap:OtherNonoperatingIncomeExpense
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_32f8298f1e794b79a00ea0dab0865073"
      unitRef="U002">187000</us-gaap:OtherNonoperatingIncomeExpense>
    <us-gaap:OtherNonoperatingIncomeExpense
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_baa0473b662842c0b6146ca6484985e5"
      unitRef="U002">3000</us-gaap:OtherNonoperatingIncomeExpense>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_eeb95e59b8334ad9a111ffc207cc4439"
      unitRef="U002">-64071000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_68a278a750c440a4b9480f5765ab69d5"
      unitRef="U002">-89739000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_e40b8d3a34a84144a801e3ecfb09d5f7"
      unitRef="U002">1094000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_ced8ef86608a400ea8e16f61515f5e49"
      unitRef="U002">130000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:NetIncomeLoss
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_7b9b6b43b3bc4f8db5f0a55a8f20450a"
      unitRef="U002">-65165000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_54f0a42c4cb7431e8cdc831d788b765d"
      unitRef="U002">-89869000</us-gaap:NetIncomeLoss>
    <us-gaap:EarningsPerShareDiluted
      contextRef="c20220101to20220331"
      decimals="2"
      id="Fact_dc072bd907c2412c85e96428b2cb98f0"
      unitRef="U004">-0.46</us-gaap:EarningsPerShareDiluted>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20220101to20220331"
      decimals="2"
      id="Fact_58fe2c982bbe4a918701a6734d89a85f"
      unitRef="U004">-0.46</us-gaap:EarningsPerShareBasic>
    <us-gaap:EarningsPerShareDiluted
      contextRef="c20210101to20210331"
      decimals="2"
      id="Fact_8d42c036be6f4f13acc78e5a8a1ea0d8"
      unitRef="U004">-0.64</us-gaap:EarningsPerShareDiluted>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20210101to20210331"
      decimals="2"
      id="Fact_88a2d2e2959347e3a70a3eb905fd197a"
      unitRef="U004">-0.64</us-gaap:EarningsPerShareBasic>
    <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_cd570838ddb649738d00df7a09fcdbb7"
      unitRef="U001">141599000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_4b2adeca36494082be5f8df1161c9e73"
      unitRef="U001">141599000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_a4cb8cf568b8421b9aef20c6f872b4fc"
      unitRef="U001">140770000</us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_d79beadf7224439dae1c75b3c3939771"
      unitRef="U001">140770000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:NetIncomeLoss
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_915ab404992b41439ff8983bc3d53452"
      unitRef="U002">-65165000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_e2219f4b91ac4074bf0182268caca6fc"
      unitRef="U002">-89869000</us-gaap:NetIncomeLoss>
    <us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_b5442f2d54144714936b29f9dc8919c3"
      unitRef="U002">-15756000</us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_9fdb4ea0ec7d4dc5b1e180547879efb8"
      unitRef="U002">-3006000</us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_8c488c3b36034e08aa370c9ffb2c6875"
      unitRef="U002">-154000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_3d7f7690411649a3a532188469a6cbe2"
      unitRef="U002">-126000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:ComprehensiveIncomeNetOfTax
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_49ad4947efda47a8b9b2ba8b913e17fd"
      unitRef="U002">-81075000</us-gaap:ComprehensiveIncomeNetOfTax>
    <us-gaap:ComprehensiveIncomeNetOfTax
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_2b15cd4eb3be402a951f50cf88199c7f"
      unitRef="U002">-93001000</us-gaap:ComprehensiveIncomeNetOfTax>
    <us-gaap:SharesIssued
      contextRef="c20201231_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_98dc7656285f417fb1c4f49b8065b1d8"
      unitRef="U001">140366000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20201231_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_c0615757be1444029ca73ff9806fdd30"
      unitRef="U002">140000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20201231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_fa026da6ce684909b5fcdddba18fbc9b"
      unitRef="U002">1895519000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20201231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_08332899ffb34f30a41a0135cd7a004c"
      unitRef="U002">-21071000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20201231_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_e1c52f1a7e044d809c116cc3f4868079"
      unitRef="U002">-1131306000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20201231"
      decimals="-3"
      id="Fact_ce774b980d1945b28dbd6dbee1aff00b"
      unitRef="U002">743282000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLoss
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_4ec345cbb3d84783ab99b6fcd9d52e13"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_ff8ba7d6607349d7a7d35878e7a4fd56"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_f8b59090577b46a5a21175e258ec3def"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_a0b1fb196c4248019f70cc81ce4ffdd3"
      unitRef="U002">-89869000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_b1aada9a3f114d9b9e11d3c420555552"
      unitRef="U002">-89869000</us-gaap:NetIncomeLoss>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_bc7eeed51da0436cbe39d0f4930cbfad"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_8485bb39a4624b6aa217322973dcb1c8"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_82090969b9fa4e518410ddb5dd7da186"
      unitRef="U002">-3006000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_6c13962c29444067a83835ea2d6a775f"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_b99f2c3965304e6bb4d58a265f3c82d8"
      unitRef="U002">-3006000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_6d20bc87313146299844f8544aba62de"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_2ef04cec7e534c4fb3679d4ee1242567"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_50b7616b414448569c7aa087a3d1acb8"
      unitRef="U002">-126000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_dbd37d1d557f42e89b78ff357c9b5dac"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_7c24435c391a46c98b5bd04d73d864f3"
      unitRef="U002">-126000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_e267472edd1048f38821b09ca0341876"
      unitRef="U001">809000</us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_09705319fad544f88f52a93356ba29e5"
      unitRef="U002">1000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_ef64f8607f344130b80bf600834f5f4e"
      unitRef="U002">7758000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_1c877cfc4bf74910b90d494f770b2a0e"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_c6498dd7baa44d219c112e112d9510a9"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_7960fc72133543c5a88516ffd647eb32"
      unitRef="U002">7759000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_54f09c577571488cb954476a599f2d5f"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_5358d98bd2504580bff7d169c068670d"
      unitRef="U002">37861000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_91408da813b4475b88f02413dac41c10"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_d80dd81bdc894762b05120404ed5933a"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_abe5472affc54cdc9a4597cd351df2b5"
      unitRef="U002">37861000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_77b5650ab39c40beb7a58c73a9893326"
      unitRef="U001">251000</us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_5f0fb82584424913812c7cbe37400a2e"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_6d19d713a97144a6a44bb652f9fda88d"
      unitRef="U002">15337000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_f6dca46437f44b63817ebf5894395adf"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20210101to20210331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_08a9b918ec4140e1a9e6142ecc878baf"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_205aa44f59224abfa0b5dd7f8960b443"
      unitRef="U002">15337000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:SharesIssued
      contextRef="c20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_46fcdfab3930406fadd6b10270850a20"
      unitRef="U001">140924000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20210331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_95ec257c7d824e90b99af68bc1f7fc7c"
      unitRef="U002">141000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20210331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_a95e0011f0b540229391e10f2c4c7add"
      unitRef="U002">1925801000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20210331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_37499af29a7b4a6e9f1602a1e385dc70"
      unitRef="U002">-24203000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20210331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_372b0e590ecb4a67982448d69ad3bba4"
      unitRef="U002">-1221175000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20210331"
      decimals="-3"
      id="Fact_9da1d58b3e7f44069fd02dc6958b717e"
      unitRef="U002">680564000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:SharesIssued
      contextRef="c20211231_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_8877c62e6b554930a9b4e66c4ff5d83c"
      unitRef="U001">141210000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20211231_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_71ee1f28a48b4912b7856878fffe6d71"
      unitRef="U002">141000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_6ca53082497a48cbbe21e6779f6c68de"
      unitRef="U002">1964167000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_74e796cf373641daa869d8d47e0c4624"
      unitRef="U002">-32668000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20211231_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_e85b208449cd4a72aab42974aaa1fde6"
      unitRef="U002">-1159903000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20211231"
      decimals="-3"
      id="Fact_59bf2f8f2caf43f4b752ed6ec5430d19"
      unitRef="U002">771737000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLoss
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_d9edf6248dc1424aafd3356543008867"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_7dd7c1f845a045a090badfcc7ab6db76"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_8c15f483d1064d24b2d9f6619420dd72"
      unitRef="U002">0</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_166de7975ba34b89a10a2e6535435fbe"
      unitRef="U002">-65165000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_e67dfd4b29294fe5a04362d945862f88"
      unitRef="U002">-65165000</us-gaap:NetIncomeLoss>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_ecabb894029043e0827e09799b634f83"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_1f8c2bf4d6034265bca78ef8f8152813"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_c252fecd225c4a61a39f2141313b069a"
      unitRef="U002">-15756000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_b9c09de5a34f49b2bfc5a8e9efcba534"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_76a2d72a1e7c4a8da884d26ad31c6802"
      unitRef="U002">-15756000</us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_06b5276b17cb47b2b6555023dab9cfec"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_d95f53b4b13f443cbd0bc435f640800e"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_4995c8f2196140e6a69b1dc2b9a5305f"
      unitRef="U002">-154000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_7a87e7f86cba4eff8c9cf38cab460812"
      unitRef="U002">0</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_3efe3a97b35e46be9a6cb637d571311c"
      unitRef="U002">-154000</us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax>
    <us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_efb172d9a80a4f9c94cd3511ed3f16e9"
      unitRef="U001">847000</us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_8ac07b9c1fe44ba7983c69266299a134"
      unitRef="U002">1000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_64beaae13e384dc7974a35c709224829"
      unitRef="U002">1848000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_7183dc09cfa54eea90ec50925a441ebc"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_28f6a3aee5dc49b0ae461653c0e378ce"
      unitRef="U002">0</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_740610803a7b4e7ebd68ee69ac2c7e96"
      unitRef="U002">1849000</us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_9897ad26311f4f30a8d313ca1f6227c7"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_7f83f4f9c68b46d5b1d2477f66dbe960"
      unitRef="U002">26236000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_93849307749e41309ff4147077bd45a2"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_a0e167b293a946898aabd539f2085050"
      unitRef="U002">0</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_6705359364e94eb6a3a9944a3bf9888c"
      unitRef="U002">26236000</us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue>
    <us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_0fd8bb9777ee47b3b343e25304e72e8f"
      unitRef="U001">304000</us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_b3a97b30724d4a72b0a88b1d62787ecf"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_5fe03c80b03541ca9c3f81e124ca7bae"
      unitRef="U002">9173000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_cb8de3379f1d415b9a6c56f54a5ffe13"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20220101to20220331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_b37f16c3895c4324a133db8ca300d70d"
      unitRef="U002">0</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_c21be2c2b9c54fd48d9752d97f10618a"
      unitRef="U002">9173000</us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:SharesIssued
      contextRef="c20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_8f9f94f1d3d940a68541e958de1f55f0"
      unitRef="U001">141753000</us-gaap:SharesIssued>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20220331_StatementEquityComponentsAxis_CommonStockMember"
      decimals="-3"
      id="Fact_0fa1ab6fe60a48e88125f45695548614"
      unitRef="U002">142000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20220331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember"
      decimals="-3"
      id="Fact_ba66578036484b5f968843707bc07ed1"
      unitRef="U002">1983078000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20220331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember"
      decimals="-3"
      id="Fact_459e8dddf67049ffbc89a031afcfb160"
      unitRef="U002">-48578000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20220331_StatementEquityComponentsAxis_RetainedEarningsMember"
      decimals="-3"
      id="Fact_f3febeb396b8498887a5e227b0d9203b"
      unitRef="U002">-1225068000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20220331"
      decimals="-3"
      id="Fact_410eb94491b24411ae562ce3bd42c127"
      unitRef="U002">709574000</us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest>
    <us-gaap:NetIncomeLoss
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_f7c36546ee144c2c86ebae7331367498"
      unitRef="U002">-65165000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_a21016941dc0429abc056d42872b32b2"
      unitRef="U002">-89869000</us-gaap:NetIncomeLoss>
    <us-gaap:Depreciation
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_100d69cecae84cbdad6e81cc7ef52262"
      unitRef="U002">3701000</us-gaap:Depreciation>
    <us-gaap:Depreciation
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_8c77ba4be59247e38c94131c141d0abf"
      unitRef="U002">3917000</us-gaap:Depreciation>
    <us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_9e6711269ac449af9f3ea5cf3d5eaa6a"
      unitRef="U002">602000</us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense>
    <us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_5558af291e4642f9823614e737f072ce"
      unitRef="U002">394000</us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense>
    <us-gaap:AmortizationOfIntangibleAssets
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_edc8ad178aa7466a8d83a15fca3ea881"
      unitRef="U002">592000</us-gaap:AmortizationOfIntangibleAssets>
    <us-gaap:AmortizationOfIntangibleAssets
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_f8039ed914974946804216d314447463"
      unitRef="U002">544000</us-gaap:AmortizationOfIntangibleAssets>
    <us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_246d1c45e9574034a56b56918f85ebb2"
      unitRef="U002">-4175000</us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments>
    <us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_4aaed7ae1baf412b9dbc761309827e6d"
      unitRef="U002">-4023000</us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments>
    <us-gaap:AmortizationOfFinancingCosts
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_0996ae3cb47d4deda2a70a7fe98905e0"
      unitRef="U002">1343000</us-gaap:AmortizationOfFinancingCosts>
    <us-gaap:AmortizationOfFinancingCosts
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_0c9f58357fb646578e9fa6d8e42f1be2"
      unitRef="U002">860000</us-gaap:AmortizationOfFinancingCosts>
    <us-gaap:ShareBasedCompensation
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_04aaa2990d5a40ad8fdb1b5232b70a08"
      unitRef="U002">26236000</us-gaap:ShareBasedCompensation>
    <us-gaap:ShareBasedCompensation
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_75990e27c7ef4862aef11ff7e8db6961"
      unitRef="U002">37861000</us-gaap:ShareBasedCompensation>
    <us-gaap:RealizedInvestmentGainsLosses
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_14350362b48c4c63a2d02245c7bdfc8e"
      unitRef="U002">10000</us-gaap:RealizedInvestmentGainsLosses>
    <us-gaap:RealizedInvestmentGainsLosses
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_1d0b4f23d12a4c8d93769c2560a353b7"
      unitRef="U002">13000</us-gaap:RealizedInvestmentGainsLosses>
    <us-gaap:GainLossOnDispositionOfAssets
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_01a5dec9e9674dcc9254b9bfa6e79949"
      unitRef="U002">-527000</us-gaap:GainLossOnDispositionOfAssets>
    <us-gaap:GainLossOnDispositionOfAssets
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_9e5576dfce9c47598f395f576a1839a2"
      unitRef="U002">0</us-gaap:GainLossOnDispositionOfAssets>
    <us-gaap:ImpairmentOfIntangibleAssetsFinitelived
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_7fcd200b638b455db39131034fdc6876"
      unitRef="U002">110000</us-gaap:ImpairmentOfIntangibleAssetsFinitelived>
    <us-gaap:ImpairmentOfIntangibleAssetsFinitelived
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_fe5c9b55fb8549bebb24e58da0204a34"
      unitRef="U002">221000</us-gaap:ImpairmentOfIntangibleAssetsFinitelived>
    <us-gaap:IncreaseDecreaseInContractWithCustomerAsset
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_16676ffc3ca64894b557287e56466f06"
      unitRef="U002">-35774000</us-gaap:IncreaseDecreaseInContractWithCustomerAsset>
    <us-gaap:IncreaseDecreaseInContractWithCustomerAsset
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_4adb47def1984cd7bbd6593823908452"
      unitRef="U002">-52807000</us-gaap:IncreaseDecreaseInContractWithCustomerAsset>
    <us-gaap:IncreaseDecreaseInInventories
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_6cc57db037e24224babb23341491fa27"
      unitRef="U002">-774000</us-gaap:IncreaseDecreaseInInventories>
    <us-gaap:IncreaseDecreaseInInventories
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_855e538885814931adc2c6ca522196ff"
      unitRef="U002">234000</us-gaap:IncreaseDecreaseInInventories>
    <us-gaap:IncreaseDecreaseInOtherOperatingAssets
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_6beef6ad7156442b8b64be1683073767"
      unitRef="U002">7222000</us-gaap:IncreaseDecreaseInOtherOperatingAssets>
    <us-gaap:IncreaseDecreaseInOtherOperatingAssets
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_6b1b789ac55944df81d7f4361d13837c"
      unitRef="U002">-16481000</us-gaap:IncreaseDecreaseInOtherOperatingAssets>
    <us-gaap:IncreaseDecreaseInAccruedIncomeTaxesPayable
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_920199b2a9f34fa1848e6eca1d94d87b"
      unitRef="U002">865000</us-gaap:IncreaseDecreaseInAccruedIncomeTaxesPayable>
    <us-gaap:IncreaseDecreaseInAccruedIncomeTaxesPayable
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_86237017148a4c7887a8ba1643288e88"
      unitRef="U002">2000</us-gaap:IncreaseDecreaseInAccruedIncomeTaxesPayable>
    <us-gaap:IncreaseDecreaseInAccountsPayable
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_8a994583ad564784b70d134601567caf"
      unitRef="U002">2878000</us-gaap:IncreaseDecreaseInAccountsPayable>
    <us-gaap:IncreaseDecreaseInAccountsPayable
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_7d0b289b5d31478faec7c1781df64a2b"
      unitRef="U002">-9569000</us-gaap:IncreaseDecreaseInAccountsPayable>
    <us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_5f5c568dfefd46649d7f965b7bc2f695"
      unitRef="U002">-22285000</us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities>
    <us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_e29dcd8047ff491884c92796c96013cb"
      unitRef="U002">-36465000</us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities>
    <us-gaap:IncreaseDecreaseInOtherCurrentLiabilities
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_08f6c9cf45f246f6a33cd0c9749cb737"
      unitRef="U002">10473000</us-gaap:IncreaseDecreaseInOtherCurrentLiabilities>
    <us-gaap:IncreaseDecreaseInOtherCurrentLiabilities
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_8da87902979a47b2b8cd9fcda264eef6"
      unitRef="U002">-11905000</us-gaap:IncreaseDecreaseInOtherCurrentLiabilities>
    <us-gaap:IncreaseDecreaseInContractWithCustomerLiability
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_5d444769c22d417199294bd747e46936"
      unitRef="U002">-25018000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
    <us-gaap:IncreaseDecreaseInContractWithCustomerLiability
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_7536a4e7a5c548658c9c6c4190e7e76b"
      unitRef="U002">-23717000</us-gaap:IncreaseDecreaseInContractWithCustomerLiability>
    <us-gaap:NetCashProvidedByUsedInOperatingActivities
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_66c31f18a56f439ab964f9bf11cd801d"
      unitRef="U002">-31650000</us-gaap:NetCashProvidedByUsedInOperatingActivities>
    <us-gaap:NetCashProvidedByUsedInOperatingActivities
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_aaaa638d546d45448755c94c63222ccd"
      unitRef="U002">-54662000</us-gaap:NetCashProvidedByUsedInOperatingActivities>
    <us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_083200534ca3433a9d3c58296e5b5402"
      unitRef="U002">462855000</us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt>
    <us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_50e0b935822448d399c6da50df573ca5"
      unitRef="U002">330051000</us-gaap:PaymentsToAcquireAvailableForSaleSecuritiesDebt>
    <us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_421423d1ea9a4d73aef63e7e59de4afb"
      unitRef="U002">178837000</us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities>
    <us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_6dc4fafd64864e3188177206b20e21e5"
      unitRef="U002">411907000</us-gaap:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities>
    <us-gaap:PaymentsToAcquirePropertyPlantAndEquipment
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_5c4c86b4988a4bcc93f568312cf27532"
      unitRef="U002">2705000</us-gaap:PaymentsToAcquirePropertyPlantAndEquipment>
    <us-gaap:PaymentsToAcquirePropertyPlantAndEquipment
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_23746708bcf2482183689f1b17ed01be"
      unitRef="U002">1772000</us-gaap:PaymentsToAcquirePropertyPlantAndEquipment>
    <us-gaap:PaymentsToAcquireIntangibleAssets
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_bedfe0d50deb453aac9adee6a16b847b"
      unitRef="U002">826000</us-gaap:PaymentsToAcquireIntangibleAssets>
    <us-gaap:PaymentsToAcquireIntangibleAssets
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_2503d109e9bf429abba6e180534abb50"
      unitRef="U002">1228000</us-gaap:PaymentsToAcquireIntangibleAssets>
    <us-gaap:NetCashProvidedByUsedInInvestingActivities
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_92cb4d2048d14989a03cc74060fe995e"
      unitRef="U002">-287549000</us-gaap:NetCashProvidedByUsedInInvestingActivities>
    <us-gaap:NetCashProvidedByUsedInInvestingActivities
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_98c358a7d9cc4f7dbda064764db082d3"
      unitRef="U002">78856000</us-gaap:NetCashProvidedByUsedInInvestingActivities>
    <us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_ddb0c2b46432418f9be1b92d0e804ae9"
      unitRef="U002">1848000</us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions>
    <us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_8bffc0bd215e4f839416df4a6531312e"
      unitRef="U002">7760000</us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions>
    <us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_b75a3de029544b8ea1fafba1be80eb98"
      unitRef="U002">9173000</us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_2013b605a8914f73b56ab03781e33c14"
      unitRef="U002">15337000</us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation>
    <us-gaap:NetCashProvidedByUsedInFinancingActivities
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_eaaca3e288be4952adf9a7f8f7bf8f92"
      unitRef="U002">-7325000</us-gaap:NetCashProvidedByUsedInFinancingActivities>
    <us-gaap:NetCashProvidedByUsedInFinancingActivities
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_af5d9d765265424f939925e68f5a2822"
      unitRef="U002">-7577000</us-gaap:NetCashProvidedByUsedInFinancingActivities>
    <us-gaap:EffectOfExchangeRateOnCashAndCashEquivalents
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_05d7fd45bf434136a2b94742f2dddc94"
      unitRef="U002">-154000</us-gaap:EffectOfExchangeRateOnCashAndCashEquivalents>
    <us-gaap:EffectOfExchangeRateOnCashAndCashEquivalents
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_44c0dad63f8b413c8cf4e5c0bbc41200"
      unitRef="U002">-126000</us-gaap:EffectOfExchangeRateOnCashAndCashEquivalents>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_381c34e8f196433d88bcc5a40e6d5ead"
      unitRef="U002">-326678000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_695ef20670484629abffb58a97885612"
      unitRef="U002">16491000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents
      contextRef="c20211231"
      decimals="-3"
      id="Fact_f005ffe7399e4372b86484b39e4de899"
      unitRef="U002">869191000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents
      contextRef="c20201231"
      decimals="-3"
      id="Fact_6c5f411c5f5446ed84bf5042679097db"
      unitRef="U002">397664000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents
      contextRef="c20220331"
      decimals="-3"
      id="Fact_22fc70baf81348a4bed7f3a0cca2d925"
      unitRef="U002">542513000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents>
    <us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents
      contextRef="c20210331"
      decimals="-3"
      id="Fact_26348b07f1404eb2b971660219ce0e2f"
      unitRef="U002">414155000</us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents>
    <us-gaap:InterestPaidNet
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_1c0954c400a1482b8ec42df7704e2f57"
      unitRef="U002">594000</us-gaap:InterestPaidNet>
    <us-gaap:InterestPaidNet
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_99a9e46f9bbe4846a09670f406e934e7"
      unitRef="U002">594000</us-gaap:InterestPaidNet>
    <us-gaap:IncomeTaxesPaid
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_e1a1dc9fdd464c8d8c36512a7e6251fb"
      unitRef="U002">2000</us-gaap:IncomeTaxesPaid>
    <us-gaap:IncomeTaxesPaid
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_85ce33dc7db749c6bac7ae7eadc1d4ee"
      unitRef="U002">2000</us-gaap:IncomeTaxesPaid>
    <ions:NonCashCapitalAndPatentExpenditures
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_e747862ab08345fcae14d5a69abc90c7"
      unitRef="U002">1344000</ions:NonCashCapitalAndPatentExpenditures>
    <ions:NonCashCapitalAndPatentExpenditures
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_b758276d9ff04fe0a8e9a80dd38bfae6"
      unitRef="U002">1876000</ions:NonCashCapitalAndPatentExpenditures>
    <us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock
      contextRef="c20220101to20220331"
      id="Text_fa51a4329a644679a99132053d097cc9">
&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;We prepared the unaudited interim condensed consolidated financial statements for the three months ended&#160;March 31, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. 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 December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In our 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;).&lt;/div&gt;
</us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock>
    <us-gaap:BasisOfAccountingPolicyPolicyTextBlock
      contextRef="c20220101to20220331"
      id="Text_81b8305cf0914dd480c3779bb834c828">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We prepared the unaudited interim condensed consolidated financial statements for the three months ended&#160;March 31, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. 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 December 31, 2021 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.&lt;/div&gt;
</us-gaap:BasisOfAccountingPolicyPolicyTextBlock>
    <us-gaap:ConsolidationPolicyTextBlock
      contextRef="c20220101to20220331"
      id="Text_c46fa5d2afe84cef91a6b400d35f4f37">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In our 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;).&lt;/div&gt;
</us-gaap:ConsolidationPolicyTextBlock>
    <us-gaap:SignificantAccountingPoliciesTextBlock
      contextRef="c20220101to20220331"
      id="Text_3f631d62f8b3441ca8993f923978bb09">
&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;"&gt;At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements&lt;/span&gt;, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. If there is no appropriate analogous authoritative accounting literature, ASC 808 suggests companies consistently apply a reasonable and rational accounting policy election. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/span&gt;. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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 January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: 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 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;, for collaborations with substantive changes that occurred in 2022. 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, 2021 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;For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 first quarter of 2022, we earned a $10 million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#x2019;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 expenses we may incur;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 number of internal hours we will spend performing these services;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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: justify; 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;Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#x2019;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;amp;A, expenses in our 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; 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;Under our distribution agreements with Sobi, Sobi is 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: 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 agreements 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. Under our agreements with Sobi, we transferred all reserves to Sobi. 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, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: 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 and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services. 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: 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;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 2021, 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 first quarter of 2022, we recognized $18 million in milestone payments when Biogen advanced two targets under our 2013 strategic collaboration. 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 first quarter of 2022.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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 2021, we earned a $60 million license fee from Biogen when Biogen licensed ION306, an investigational medicine in development to treat SMA.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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. For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.&lt;/div&gt;

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

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

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

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

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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: left; 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Eplontersen Collaboration with AstraZeneca&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had one performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. As we continue to lead the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;amp;A expense and R&amp;amp;D expense, respectively. Refer to Item 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Management&#x2019;s Discussion and Analysis of Financial Condition and Results of Operations&lt;/span&gt;, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. &lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: 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, 2022, approximately 82.2 percent of our contracts receivables were from two significant customers. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two significant customers.&lt;/div&gt;

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

&lt;div style="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, 2022 and 2021, we recognized $26.2 million and $26.0 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, 2022, we held equity investments in three publicly held companies, Antisense Therapeutics Limited, or ATL, Bicycle Therapeutics plc, or Bicycle, and ProQR Therapeutics N.V., or ProQR. We also held equity investments in seven privately held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, YourBio Health, Inc. (formerly 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 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. As a result of these observable price changes, we recognized a total gain of $14.8 million on our investments in these companies 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. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We recorded an immaterial amount of inventory write-offs for the three months ended&#160;March 31, 2022 and 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 31, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- clinical&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- commercial&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,165&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total raw materials&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,929&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,637&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;466&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;390&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,806&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;div style="display:none;"&gt;&lt;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 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="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#x2019;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $9.6 million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.&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 expected to be realized.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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="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;Basic and Diluted Net Loss Per Share&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our basic net loss per share for the three months ended&#160;March 31, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended March 31, 2022 and 2021 were $0.46 and $0.64, respectively.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-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, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td 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, or 0.125% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three months ended&#160;March 31, 2021, common stock from our 1 percent convertible senior notes, or 1% Notes, would also have had an anti-dilutive effect on net loss per share.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three months ended&#160;March 31, 2022, common stock from the following would also have had an anti-dilutive effect on net loss per share:&lt;/div&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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% Notes.&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, 2022, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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;"&gt;We account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability on our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our 0% and 0.125% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our 0% and 0.125% Notes over the respective contractual term using an effective interest rate of 0.5 percent for each note. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Convertible Debt&lt;/span&gt;, for further details on our convertible debt instruments.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the issuance of our 0% Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the 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;We operate as a &lt;span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e"&gt;single&lt;/span&gt; segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our 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.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;55.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: 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;6.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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;In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the three months ended March 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;0.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;50.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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, 2022 was $33.08 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 PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other executive officers. 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 the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our executive officers for the three months ended&#160;March 31, 2022 and 2021 were $42.28 and $77.17 per share, 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 table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2022 and 2021 (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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;160&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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;19,082&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;/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;6,994&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;/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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,236&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;/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, 2022, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $67.7 million, $69.2 million and $5.4 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, 1.7 years and 1.6 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;We do not expect any recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:SignificantAccountingPoliciesTextBlock>
    <us-gaap:RevenueFromContractWithCustomerPolicyTextBlock
      contextRef="c20220101to20220331"
      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;"&gt;At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements&lt;/span&gt;, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. If there is no appropriate analogous authoritative accounting literature, ASC 808 suggests companies consistently apply a reasonable and rational accounting policy election. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/span&gt;. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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 January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: 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 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;, for collaborations with substantive changes that occurred in 2022. 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, 2021 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;For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 first quarter of 2022, we earned a $10 million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson&#x2019;s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 expenses we may incur;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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 number of internal hours we will spend performing these services;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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: justify; 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;Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi&#x2019;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&amp;amp;A, expenses in our 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; 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;Under our distribution agreements with Sobi, Sobi is 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: 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 agreements 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. Under our agreements with Sobi, we transferred all reserves to Sobi. 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, 2021 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: 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 and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services. 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: 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;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 2021, 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 first quarter of 2022, we recognized $18 million in milestone payments when Biogen advanced two targets under our 2013 strategic collaboration. 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 first quarter of 2022.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;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 2021, we earned a $60 million license fee from Biogen when Biogen licensed ION306, an investigational medicine in development to treat SMA.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; 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. For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.&lt;/div&gt;

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

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

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

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

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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: left; 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Eplontersen Collaboration with AstraZeneca&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had one performance obligation.&#160; For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. As we continue to lead the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&amp;amp;A expense and R&amp;amp;D expense, respectively. Refer to Item 2, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Management&#x2019;s Discussion and Analysis of Financial Condition and Results of Operations&lt;/span&gt;, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca. &lt;/div&gt;
</us-gaap:RevenueFromContractWithCustomerPolicyTextBlock>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_Ion859Member"
      decimals="-6"
      id="Fact_c66a5241a21143ed8f3a497ac21b877d"
      unitRef="U002">10000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:UpfrontPaymentReceived
      contextRef="c20181001to20181231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember"
      decimals="-6"
      id="Fact_72588160d9344e3d91319fe6a66f7d24"
      unitRef="U002">75000000</ions:UpfrontPaymentReceived>
    <ions:UpfrontPaymentReceived
      contextRef="c20181001to20181231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember"
      decimals="-6"
      id="Fact_df2e1cb511f24d2a84b6cc2d7d4dc617"
      unitRef="U002">75000000</ions:UpfrontPaymentReceived>
    <ions:RevenueFromContractWithCustomerTransactionPriceAdditions
      contextRef="c20211001to20211231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember"
      decimals="-5"
      id="Fact_4419a9d643c14dde9c2d40f4d61b0e4c"
      unitRef="U002">7500000</ions:RevenueFromContractWithCustomerTransactionPriceAdditions>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember"
      decimals="-6"
      id="Fact_94ca715aaad045a79c4d7f4d005942f7"
      unitRef="U002">18000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:NumberOfTargetsAdvanced
      contextRef="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember"
      decimals="INF"
      id="Fact_f2258c9c40f845b4bb100ba3ef3051b5"
      unitRef="U005">2</ions:NumberOfTargetsAdvanced>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20211001to20211231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember"
      decimals="-6"
      id="Fact_13676dd08f854acb99df553544328759"
      unitRef="U002">60000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="-5"
      id="Fact_d95ecd0c2d0e4ea494c6592f2153d064"
      unitRef="U002">41200000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:NumberOfAgreementsWithCollaborationPartner
      contextRef="c20180401to20180630_MajorCustomersAxis_BiogenIncMember"
      decimals="INF"
      id="Fact_c0d9a811936e47c2b113f70412abe1a4"
      unitRef="U006">2</ions:NumberOfAgreementsWithCollaborationPartner>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="-6"
      id="Fact_53da6e65fb0741c483420c0238104ade"
      unitRef="U002">200000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:NumberOfMaterialComponents
      contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="INF"
      id="Fact_b27e54c14e90416580647f971d492180"
      unitRef="U007">4</ions:NumberOfMaterialComponents>
    <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations
      contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="INF"
      id="Fact_e8e1aec533f84dbf98a2133cce0f7dc7"
      unitRef="U008">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
    <ions:RevenueFromContractWithCustomerTransactionPrice
      contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="-6"
      id="Fact_387a94400e2542adb3feef5e16cbd22c"
      unitRef="U002">200000000</ions:RevenueFromContractWithCustomerTransactionPrice>
    <ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner
      contextRef="c20220101to20220331_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="2"
      id="Fact_3165c6664dcc46f6bd3fb9a729593495"
      unitRef="U003">0.55</ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner>
    <us-gaap:ReceivablesPolicyTextBlock
      contextRef="c20220101to20220331"
      id="Text_65525657713c48478f6f26b531ff73b7">
&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, 2022, approximately 82.2 percent of our contracts receivables were from two significant customers. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two significant customers.&lt;/div&gt;
</us-gaap:ReceivablesPolicyTextBlock>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20220101to20220331_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember"
      decimals="3"
      id="Fact_ddb9c9779caa4c7ba7a8628627b81f91"
      unitRef="U003">0.822</us-gaap:ConcentrationRiskPercentage1>
    <ions:NumberOfSignificantCustomers
      contextRef="c20220101to20220331"
      decimals="INF"
      id="Fact_1a88c8e3635d4a64afd7542090bb8bb4"
      unitRef="U009">2</ions:NumberOfSignificantCustomers>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember"
      decimals="3"
      id="Fact_2797753f496a4c3a9e250ecbc9db8bec"
      unitRef="U003">0.938</us-gaap:ConcentrationRiskPercentage1>
    <ions:NumberOfSignificantCustomers
      contextRef="c20210101to20211231"
      decimals="INF"
      id="Fact_61c499808edf4f65970284a4fd7b4782"
      unitRef="U009">2</ions:NumberOfSignificantCustomers>
    <us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy
      contextRef="c20220101to20220331"
      id="Text_6f3107eba95140ffb1c98fd3296491db">
&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;
</us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy>
    <us-gaap:RevenueRecognitionPolicyTextBlock
      contextRef="c20220101to20220331"
      id="Text_1fffd2b34a31436fa2700206d4f2a54a">
&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, 2022 and 2021, we recognized $26.2 million and $26.0 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="c20220101to20220331"
      decimals="-5"
      id="Fact_29a96e3cb4bb4440a9a1b2cd97733561"
      unitRef="U002">26200000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20210101to20210331"
      decimals="-5"
      id="Fact_9b7323eabb394f1aa269712264f74431"
      unitRef="U002">26000000.0</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:CostOfSalesPolicyTextBlock
      contextRef="c20220101to20220331"
      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="c20220101to20220331"
      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, 2022, we held equity investments in three publicly held companies, Antisense Therapeutics Limited, or ATL, Bicycle Therapeutics plc, or Bicycle, and ProQR Therapeutics N.V., or ProQR. We also held equity investments in seven privately held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, YourBio Health, Inc. (formerly 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 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. As a result of these observable price changes, we recognized a total gain of $14.8 million on our investments in these companies in our condensed consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.&lt;/div&gt;
</us-gaap:InvestmentPolicyTextBlock>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20220331"
      decimals="INF"
      id="Fact_8037e90f29fb43ae9797ff009a688387"
      unitRef="U010">3</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20220331"
      decimals="INF"
      id="Fact_e003aeab75174162b833cf14b3a44106"
      unitRef="U010">7</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued
      contextRef="c20200101to20201231"
      decimals="INF"
      id="Fact_1d052d9ce42e45d89c9a5e9b00144f66"
      unitRef="U011">3</ions:NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued>
    <us-gaap:GainLossOnInvestments
      contextRef="c20200101to20201231_FinancialInstrumentAxis_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember"
      decimals="-5"
      id="Fact_e09e9575233b4dcfb1b480c449770f50"
      unitRef="U002">14800000</us-gaap:GainLossOnInvestments>
    <us-gaap:InventoryPolicyTextBlock
      contextRef="c20220101to20220331"
      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. Our raw materials - commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials - commercial inventory.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. We recorded an immaterial amount of inventory write-offs for the three months ended&#160;March 31, 2022 and 2021.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 31, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- clinical&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- commercial&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,165&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total raw materials&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,929&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,637&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;466&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;390&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,806&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:InventoryPolicyTextBlock>
    <us-gaap:ScheduleOfInventoryCurrentTableTextBlock
      contextRef="c20220101to20220331"
      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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"/&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 31, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 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, 2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials:&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- clinical&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,764&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,507&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- commercial&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,165&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total raw materials&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,929&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,646&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,637&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;466&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;390&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;&lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,032&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,806&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfInventoryCurrentTableTextBlock>
    <us-gaap:InventoryRawMaterials
      contextRef="c20220331_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_3043726b7f0d40479abbe8c68900b93f"
      unitRef="U002">15764000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20211231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_6cec13c5f4334a1ba6216a6bc406747c"
      unitRef="U002">14507000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20220331_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_4a8280762bb1470eace824e402d6b623"
      unitRef="U002">2165000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20211231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_cf1accaf2b004921b424e5cd65e40c1f"
      unitRef="U002">4139000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20220331"
      decimals="-3"
      id="Fact_9975fb0b2fa74f9e8ab81ebad8fb2237"
      unitRef="U002">17929000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20211231"
      decimals="-3"
      id="Fact_e3f1efde1cdb414796dec720e17eac54"
      unitRef="U002">18646000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20220331"
      decimals="-3"
      id="Fact_e7c4b729eb5c4047a12ddaf1f657b647"
      unitRef="U002">5637000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20211231"
      decimals="-3"
      id="Fact_182d548d120f4e1daae74044c3e1bbe5"
      unitRef="U002">5770000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20220331"
      decimals="-3"
      id="Fact_b21c128f10e14f89b4963ecd92676ea1"
      unitRef="U002">466000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20211231"
      decimals="-3"
      id="Fact_70a3a016ecb849cd9021230823cf224d"
      unitRef="U002">390000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryNet
      contextRef="c20220331"
      decimals="-3"
      id="Fact_6f6a7ebaae1b4d95ace7fcfcf1fba210"
      unitRef="U002">24032000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20211231"
      decimals="-3"
      id="Fact_3e4c02edf53745679ae7e698216e7837"
      unitRef="U002">24806000</us-gaap:InventoryNet>
    <us-gaap:LesseeLeasesPolicyTextBlock
      contextRef="c20220101to20220331"
      id="Text_e6ea38e98e2c41b6b3353d330002d1c3">
&lt;div style="display:none;"&gt;&lt;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 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="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant&#x2019;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $9.6 million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.&lt;/div&gt;
</us-gaap:LesseeLeasesPolicyTextBlock>
    <ions:LesseeOperatingLeaseFreeRentPeriod
      contextRef="c20220101to20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember"
      id="Fact_47d0951dc5cf46abb2ab61b44a977bad">P7M</ions:LesseeOperatingLeaseFreeRentPeriod>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue
      contextRef="c20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember"
      decimals="-5"
      id="Fact_6e9e11d907a042dcbbbf9300319016c9"
      unitRef="U002">9600000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
    <us-gaap:ResearchAndDevelopmentExpensePolicy
      contextRef="c20220101to20220331"
      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="c20220101to20220331"
      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="c20220101to20220331"
      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 expected to be realized.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.&lt;/div&gt;
</us-gaap:IncomeTaxPolicyTextBlock>
    <us-gaap:ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock
      contextRef="c20220101to20220331"
      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="c20220101to20220331"
      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="c20220101to20220331"
      id="Text_d8ae7016e11e44938c278329c28c5334">
&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;Basic and Diluted Net Loss Per Share&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our basic net loss per share for the three months ended&#160;March 31, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended March 31, 2022 and 2021 were $0.46 and $0.64, respectively.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-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, 2022 and 2021, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td 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, or 0.125% Notes;&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three months ended&#160;March 31, 2021, common stock from our 1 percent convertible senior notes, or 1% Notes, would also have had an anti-dilutive effect on net loss per share.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the three months ended&#160;March 31, 2022, common stock from the following would also have had an anti-dilutive effect on net loss per share:&lt;/div&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 36pt;"/&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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% Notes.&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, 2022, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/div&gt;
</us-gaap:EarningsPerSharePolicyTextBlock>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20220101to20220331"
      decimals="2"
      id="Fact_aab817918ee7462eafc4e0247e0ea5c8"
      unitRef="U004">-0.46</us-gaap:EarningsPerShareBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20210101to20210331"
      decimals="2"
      id="Fact_58043c7336904e8090a7cbe86199682a"
      unitRef="U004">-0.64</us-gaap:EarningsPerShareBasic>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_e04081c13bbe48d3bb9b3d0cca81d860"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_eccc4161cecb4e0e9bd2f79ccde27795"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_2d011315162b43398edc4d43f61dfe90"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_040223863f694143aeafc77acbcabb62"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_00ed48c13a3e41a59f57e78e32a2e336"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_5765a5913d9b40179d92f2285226cd54"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_ee8886a9310f4ddcb2b7947762657218"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20210331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_792fe9322e4d409886378b2e066f65f0"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_acf69492fc724c92b962b1e11e2eaa4d"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_0a206797b8c743759065e28eac72a546"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_f1a39fa9afdb444ca040fa8fd4e57b4a"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_2ad3f2367557405a8c6d2324e912a59a"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_abddc1cdda9749a6b8af5dd8ac5eb3c8"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtPolicyTextBlock
      contextRef="c20220101to20220331"
      id="Text_6c532e56086147ee8142945e5d038e81">
&lt;div style="display:none;"&gt;&lt;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;"&gt;We account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability on our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our 0% and 0.125% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our 0% and 0.125% Notes over the respective contractual term using an effective interest rate of 0.5 percent for each note. Refer to Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Convertible Debt&lt;/span&gt;, for further details on our convertible debt instruments.&lt;/div&gt;
</us-gaap:DebtPolicyTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_fa35c62ae15545fda47bd92f0ec9050d"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_dfae12bf8c0d4b1fa86a0ad27d83e519"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_4104add5953b45b09004aee6e573d81f"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_23f33708bb144c8896edb768bcc0da12"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="3"
      id="Fact_1f8672f0057c4cd3ba9ee1a3d610959e"
      unitRef="U003">0.005</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="3"
      id="Fact_63df7b45bec94d108f6f2369726dcb1c"
      unitRef="U003">0.005</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:DerivativesPolicyTextBlock
      contextRef="c20220101to20220331"
      id="Text_2e3f06f0c3b242259c5e79489eed6c80">
&lt;div style="display:none;"&gt;&lt;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% Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the 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;
</us-gaap:DerivativesPolicyTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_2de199144db84606922afa28c32d16ec"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_f0716a76728945aeacfc77c73b2d1ec7"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:SegmentReportingPolicyPolicyTextBlock
      contextRef="c20220101to20220331"
      id="Text_a592a963d50b4e51a05a26c3eb689d06">
&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;We operate as a &lt;span style="-sec-ix-hidden:Fact_ba6a4e8bb35940dbbf919d263b57d70e"&gt;single&lt;/span&gt; segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.&lt;/div&gt;
</us-gaap:SegmentReportingPolicyPolicyTextBlock>
    <us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy
      contextRef="c20220101to20220331"
      id="Text_fabff55575924204ab4d0d1a53d5fb8f">
&lt;div style="display:none;"&gt;&lt;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, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our 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.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&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, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;55.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: 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;6.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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;In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the three months ended March 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;0.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;50.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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, 2022 was $33.08 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 PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other executive officers. 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 the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to our executive officers for the three months ended&#160;March 31, 2022 and 2021 were $42.28 and $77.17 per share, 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 table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2022 and 2021 (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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;160&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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;19,082&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;/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;6,994&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;/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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,236&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;/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, 2022, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $67.7 million, $69.2 million and $5.4 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, 1.7 years and 1.6 years, respectively.&lt;/div&gt;
</us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy>
    <us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock
      contextRef="c20220101to20220331"
      id="Text_bd2546acd7db40c8a7bd10022a59ff6d">
&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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.7&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;55.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: 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;6.3 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 years&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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;In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the three months ended March 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      decimals="3"
      id="Fact_ffb253cdaa2c497d9f158f41530bd3b8"
      unitRef="U003">0.017</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      decimals="3"
      id="Fact_e90f6a95b57e4e9785b5740f296f22cb"
      unitRef="U003">0.005</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      decimals="3"
      id="Fact_7dae66b76386466dbd8280f7df578286"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      decimals="3"
      id="Fact_6fd1d504e21a42f18d1513595b6d94a7"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      decimals="3"
      id="Fact_6c30560991c34955ac78828b469d91f7"
      unitRef="U003">0.552</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      decimals="3"
      id="Fact_470fb7c2bc154d46b527889f6bc045b5"
      unitRef="U003">0.551</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      id="Fact_e3f0b01c2b014194af0169f71cb6cace">P6Y3M18D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      id="Fact_c25f6066e793481b89742397fce1babb">P4Y10M24D</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod
      contextRef="c20220101to20220331_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member"
      id="Fact_b2ac901653d54e2fadb1e34420e76d70">P7Y</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod
      contextRef="c20220101to20220331_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember"
      id="Fact_658bc4cd50024cbc9d7a903e428fbe7f">P10Y</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod>
    <us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock
      contextRef="c20220101to20220331"
      id="Text_ed6872a6ffbb45b4b4afd44a763ec080">
&lt;div style="display:none;"&gt;&lt;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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;0.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 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;50.2&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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;
</us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_77dd56e1caba4fc6aea5e9e6e638ae5c"
      unitRef="U003">0.006</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate
      contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_4d0a456ae4dc4871b24fbb25908cd45b"
      unitRef="U003">0.001</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_6ca23795eddd40b2a9ffe6e5b60ab59e"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate
      contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_c44f5d5a2f164df58a55c39c846c87a6"
      unitRef="U003">0.000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_bd9236668f60473db27e250b8060dc0d"
      unitRef="U003">0.502</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate
      contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockMember"
      decimals="3"
      id="Fact_b5d4da261dad4007b283535f0efbd4b2"
      unitRef="U003">0.391</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockMember"
      id="Fact_4cc29778c0e447968d90cd4b1be3691e">P6M</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1
      contextRef="c20210101to20210331_AwardTypeAxis_EmployeeStockMember"
      id="Fact_6e6a732476bd479cad0b8af2fbcf4659">P6M</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1
      contextRef="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      id="Fact_27893998ace24d7cb0e5fa8a728fcf92">P4Y</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1
      contextRef="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MaximumMember"
      id="Fact_0b9e4755a19545e988f3c011792dba0c">P4Y</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1
      contextRef="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember_RangeAxis_MinimumMember"
      id="Fact_6ad8053af26d4d419b4294b9cd273b8f">P1Y</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue
      contextRef="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember"
      decimals="2"
      id="Fact_7654fd0b1d374d55b0c76914d3cd1ad7"
      unitRef="U004">33.08</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
    <ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember"
      decimals="INF"
      id="Fact_22182278d2c74c399b1aa1ec24dcb90a"
      unitRef="U013">3</ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember"
      id="Fact_eaaa26558fcd4695b1458629faf19186">P3Y</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1>
    <ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember"
      decimals="INF"
      id="Fact_a18106d46f494438a0e064c9f9a96fbd"
      unitRef="U001">0</ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest>
    <ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember"
      decimals="INF"
      id="Fact_2200a3292de944e78e0d6c8d840bacb1"
      unitRef="U003">0</ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest>
    <ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember"
      decimals="2"
      id="Fact_ce7480294faa46eab25c9b702916942c"
      unitRef="U003">1.50</ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember"
      decimals="2"
      id="Fact_f686380f406d44659451af43ea4a98c6"
      unitRef="U004">42.28</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue
      contextRef="c20210101to20210331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember"
      decimals="2"
      id="Fact_f37b71af46f844b7971b1a2b89993315"
      unitRef="U004">77.17</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
    <us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock
      contextRef="c20220101to20220331"
      id="Text_e92c56e869754c4ead60123e84fe8e44">
&lt;div style="display:none;"&gt;&lt;br/&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, 2022 and 2021 (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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;160&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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;19,082&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;/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;6,994&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;/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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,236&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;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;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20220101to20220331_IncomeStatementLocationAxis_CostOfSalesMember"
      decimals="-3"
      id="Fact_99e0a32e2d2345afb5dae8769531813a"
      unitRef="U002">160000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20210101to20210331_IncomeStatementLocationAxis_CostOfSalesMember"
      decimals="-3"
      id="Fact_40be1fccef3b4d09a3e3fd20a32e9617"
      unitRef="U002">182000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20220101to20220331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember"
      decimals="-3"
      id="Fact_d17f71a28c014450810cc3b1536b5b8b"
      unitRef="U002">19082000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20210101to20210331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember"
      decimals="-3"
      id="Fact_3c2e5d8e247446ac9584c5c2161ac0d5"
      unitRef="U002">25899000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20220101to20220331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"
      decimals="-3"
      id="Fact_10a81038cb0946ad979fbbbc68e8f89e"
      unitRef="U002">6994000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20210101to20210331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"
      decimals="-3"
      id="Fact_763195b2b34c488bb094472395ab650d"
      unitRef="U002">11780000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20220101to20220331"
      decimals="-3"
      id="Fact_86792c009d4e41b3a08f1d4f8e56e11b"
      unitRef="U002">26236000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20210101to20210331"
      decimals="-3"
      id="Fact_dff8aaed89804850bc5c9157ed3f5de6"
      unitRef="U002">37861000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions
      contextRef="c20220331_AwardTypeAxis_EmployeeStockOptionMember"
      decimals="-5"
      id="Fact_6ffe2ab146ea4bd888ad8a1bb3fc3738"
      unitRef="U002">67700000</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions
      contextRef="c20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      decimals="-5"
      id="Fact_221a3013ba19446cad9c335f9391fa1a"
      unitRef="U002">69200000</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions
      contextRef="c20220331_AwardTypeAxis_PerformanceSharesMember"
      decimals="-5"
      id="Fact_1a5a87c9d0c04b5799a90b3d2965c63f"
      unitRef="U002">5400000</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1
      contextRef="c20220101to20220331_AwardTypeAxis_EmployeeStockOptionMember"
      id="Fact_13a68deb2d8d496a9b99b31f4abcfe12">P1Y4M24D</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1
      contextRef="c20220101to20220331_AwardTypeAxis_RestrictedStockUnitsRSUMember"
      id="Fact_94356ff2a4564b669110ba6365630dc9">P1Y8M12D</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1
      contextRef="c20220101to20220331_AwardTypeAxis_PerformanceSharesMember"
      id="Fact_715166969b8f40d5bb56857e5eca4ce6">P1Y7M6D</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1>
    <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock
      contextRef="c20220101to20220331"
      id="Text_8374d619cf954b9fa63d83447841042a">
&lt;div style="display:none;"&gt;&lt;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;We do not expect any recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
    <us-gaap:InvestmentTextBlock
      contextRef="c20220101to20220331"
      id="Text_b6e1a67fcacc41d1be3b24f234df60ad">
&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, 2022:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;One year&lt;/span&gt; or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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 &lt;span style="text-indent: 0pt;"&gt;one year&lt;/span&gt; but within &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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 &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt; but within &lt;span style="text-indent: 0pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797"&gt;three and a half years&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&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, 2022, 93 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, 2022, we had an ownership interest of less than 20 percent in seven private companies and three public companies with which we conduct business. The privately held companies are Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, YourBio Health, Inc. and Suzhou-Ribo Life Science Co, Ltd. The publicly traded companies are Antisense Therapeutics Ltd., Bicycle and ProQR.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments (in thousands):&lt;/div&gt;

&lt;div 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;"&gt;Amortized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;March 31, 2022&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&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 (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;420,081&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;131&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,766&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;418,446&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;34,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;(49&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,358&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;330,358&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,133&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;329,226&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;&#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;158,548&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(376&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;158,173&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;6,419&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;(99&lt;/div&gt;&lt;/td&gt;
    &lt;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;6,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;949,813&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;133&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(3,423&lt;/div&gt;&lt;/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;946,523&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;345,813&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,275&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;335,562&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;72,844&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,974&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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;164,040&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,544&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;161,566&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,995&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(818&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', 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;34,177&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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 securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;617,692&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;94&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(15,611&lt;/div&gt;&lt;/td&gt;
    &lt;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;602,175&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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: 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;" valign="bottom"&gt;&#160;&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,567,505&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;227&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(19,034&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,548,698&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;&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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;3,946&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,274&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;11,569&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,822&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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 equity securities&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;35,012&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;20,653&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,274&lt;/div&gt;&lt;/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;51,391&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 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; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,602,517&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,880&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,308&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,600,089&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;"&gt;Amortized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;December 31, 2021&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&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 (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383,870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384,372&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&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;48,493&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,494&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,424&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,360&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(37&lt;/div&gt;&lt;/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;134,778&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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 securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;612,557&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;792&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(345&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;613,004&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;382,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,644&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;379,687&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,935&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(561&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,374&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,635&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(500&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,274&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,909&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(224&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,686&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(37&lt;/div&gt;&lt;/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;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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 securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;638,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;471&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,966&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;635,120&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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;" valign="bottom"&gt;&#160;&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,251,172&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,263&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,311&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,248,124&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; 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;&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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,145&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;18,205&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;Total equity securities included in deposits and other assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,322&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,512&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; 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;23,852&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(837&lt;/div&gt;&lt;/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;50,527&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: 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; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,278,684&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,115&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,148&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,298,651&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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;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" style="font-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;Our equity securities included in other current assets consisted of our investments in two publicly traded companies, ProQR and Bicycle, which we classify as Level 1 and Level 3 investments, respectively. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2022, we recognized a $3.4 million and a $3.2 million unrealized loss on our condensed consolidated statement of operations related to our investments in ProQR and Bicycle, respectively. In the three months ended March 31, 2021, our equity securities included in other current assets only consisted of ProQR.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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;&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, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (in thousands, except for number of investments). We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Less than 12 Months of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;More than 12 Months of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Temporary&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;337&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;647,390&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,694&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,300&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;658,690&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(12,041&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;95,543&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,697&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,685&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-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;(326&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,228&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;44&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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;406,747&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,539&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,860&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;(138&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;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;411,607&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,677&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;619&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-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;173,537&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,096&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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,455&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;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;(98&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,992&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,194&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;1,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;(16&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,005&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;(83&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;(99&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,017&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,324,532&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18,042&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;36,305&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(992&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,360,837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(19,034&lt;/div&gt;&lt;/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="c20220101to20220331"
      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, 2022:&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 46.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;One year&lt;/span&gt; or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;63&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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 &lt;span style="text-indent: 0pt;"&gt;one year&lt;/span&gt; but within &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;30&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, 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 &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt; but within &lt;span style="text-indent: 0pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797"&gt;three and a half years&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&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
      contextRef="c20220101to20220331"
      id="Fact_4b3282e6abbf4694b90d56a12cb3a78d">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage
      contextRef="c20220331"
      decimals="2"
      id="Fact_26a36804df4340729bec0b2f463acda4"
      unitRef="U003">0.63</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage>
    <ions:MaximumContractMaturityPeriodRange1
      contextRef="c20220101to20220331"
      id="Fact_3bd993e525784a5398b297b7856fe228">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20220101to20220331"
      id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage
      contextRef="c20220331"
      decimals="2"
      id="Fact_b3c2ee50dd694d208197df43360458a9"
      unitRef="U003">0.30</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20220101to20220331"
      id="Fact_812c571149d64b329fe4410606d76c7a">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage
      contextRef="c20220331"
      decimals="2"
      id="Fact_8cd01e7f5688446294ec6f1b2d7e38df"
      unitRef="U003">0.07</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage
      contextRef="c20220331"
      decimals="2"
      id="Fact_6217a171f5784696968b178278e97ffa"
      unitRef="U003">1</ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage
      contextRef="c20220331"
      decimals="2"
      id="Fact_ecfa1cb8a4484b48a192e8436b1431fe"
      unitRef="U003">0.93</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20220101to20220331"
      id="Fact_34c87d75876e42c988ffebc06f56b6a3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20220331"
      decimals="INF"
      id="Fact_b7edbc55e46842cb916a4ced56279788"
      unitRef="U010">7</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20220331"
      decimals="INF"
      id="Fact_8144a98eb4174391a5f3065f3f804da4"
      unitRef="U010">3</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock
      contextRef="c20220101to20220331"
      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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;"&gt;Amortized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;March 31, 2022&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&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 (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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;420,081&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;131&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,766&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;418,446&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;34,407&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;(49&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,358&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;330,358&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,133&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;329,226&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;&#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;158,548&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(376&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;158,173&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;6,419&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-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;(99&lt;/div&gt;&lt;/td&gt;
    &lt;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;6,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: 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;949,813&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;133&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(3,423&lt;/div&gt;&lt;/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;946,523&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;345,813&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,275&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;335,562&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;72,844&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,974&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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;164,040&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,544&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;161,566&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,995&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(818&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', 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;34,177&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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 securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;617,692&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;94&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(15,611&lt;/div&gt;&lt;/td&gt;
    &lt;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;602,175&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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: 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;" valign="bottom"&gt;&#160;&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,567,505&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;227&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(19,034&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,548,698&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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;&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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;3,946&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,274&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;11,569&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,822&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-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 equity securities&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;35,012&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;20,653&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,274&lt;/div&gt;&lt;/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;51,391&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: 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; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,602,517&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,880&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,308&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,600,089&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-indent: 6.5pt;"&gt;Amortized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;December 31, 2021&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&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 (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383,870&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(226&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384,372&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&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;48,493&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,494&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,424&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(64&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,360&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,770&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;45&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(37&lt;/div&gt;&lt;/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;134,778&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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 securities with a maturity of one year or less&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;612,557&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;792&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(345&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;613,004&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;382,000&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,644&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;379,687&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,935&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(561&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,374&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,635&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(500&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,274&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,909&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(224&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,686&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,136&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(37&lt;/div&gt;&lt;/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;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="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 securities with a maturity of more than one year&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;638,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;471&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,966&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;635,120&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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;" valign="bottom"&gt;&#160;&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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,251,172&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,263&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,311&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;1,248,124&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; 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;&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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,145&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;18,205&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;Total equity securities included in deposits and other assets (3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,615&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,707&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,322&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,512&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; 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;23,852&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;(837&lt;/div&gt;&lt;/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;50,527&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: 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; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,278,684&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,115&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,148&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,298,651&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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;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" style="font-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;Our equity securities included in other current assets consisted of our investments in two publicly traded companies, ProQR and Bicycle, which we classify as Level 1 and Level 3 investments, respectively. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2022, we recognized a $3.4 million and a $3.2 million unrealized loss on our condensed consolidated statement of operations related to our investments in ProQR and Bicycle, respectively. In the three months ended March 31, 2021, our equity securities included in other current assets only consisted of ProQR.&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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;&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;
</us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_7842515e18104a5cafcff84ddb01d951"
      unitRef="U002">420081000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_c7e1b54bc6f94cda93f41712a4a9675c"
      unitRef="U002">131000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_6987932b0c734a95908cba3dde93f730"
      unitRef="U002">1766000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_35d357c29e5b420daf82588703d78d8d"
      unitRef="U002">418446000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_80e0d5c6be1c4870adc06685000bf257"
      unitRef="U002">34407000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_18ba7ad7166c418da8278eb1c1894a6f"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_e9cc451da55c4d1c9aa3ad82c7ca9aae"
      unitRef="U002">49000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_9e8a5c54173d453cb9fb728033354336"
      unitRef="U002">34358000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_17f5c15fd8fe452b890ee866cfaa6b85"
      unitRef="U002">330358000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_45e8bcb24cc241f2bf8f293a9b67a6a6"
      unitRef="U002">1000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_36dcce36e9b446bcb8f2877352fd5851"
      unitRef="U002">1133000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_cf007fb70961423eb9a3dd191872008b"
      unitRef="U002">329226000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_7c05793868aa4afb94fcfb88fcffcb2b"
      unitRef="U002">158548000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_6c641805a540462f9d84d76f2727c1e9"
      unitRef="U002">1000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_3e3856bd21754e01ab011686088d0aa5"
      unitRef="U002">376000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_893fcba0e0004d12b5940266add3822a"
      unitRef="U002">158173000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_119b425fc08349cfbe3d5f2787dfca82"
      unitRef="U002">6419000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_60331df909a04d32a24d6b9d5d17cd03"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_e14c8b798e654a2ab567476189066f11"
      unitRef="U002">99000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_48196ae3d4df4f8195e5c9e5179b69ee"
      unitRef="U002">6320000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_3e165eb36915445a94e7bca3626be047"
      unitRef="U002">949813000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_3c026731cf6c4d2c9f3bb6487eb52874"
      unitRef="U002">133000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_cbaf34a8cf1344ed8d1c9bd3764052c6"
      unitRef="U002">3423000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_401ef7ec0ee84b33b734c6646f73945d"
      unitRef="U002">946523000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_e739ce406a594fdab205b3f709378b35"
      unitRef="U002">345813000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_1465e0f748cd4bfaa10d9f2bc25757c3"
      unitRef="U002">24000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_28d6823308c14eabb012545df1bbf47e"
      unitRef="U002">10275000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_dff0a77ea162428eac31903b7ae1af1c"
      unitRef="U002">335562000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_4069992e62e44ec39ab5806e1ac879fa"
      unitRef="U002">72844000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_13b8b3118986468c94cef784db3d7d85"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_8c034ba7ebd94e519637bf63e04e1b9f"
      unitRef="U002">1974000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_907c5df34a09413bb109221fad1ea266"
      unitRef="U002">70870000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_e43e28c5271b42a889a3b5a4967cc28d"
      unitRef="U002">164040000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_4a47ab58cf674aa491198b0931ea7362"
      unitRef="U002">70000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_54bac431fed2433b9abbb4c98f4e8737"
      unitRef="U002">2544000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_df46987f0ff442a68229243874a3a796"
      unitRef="U002">161566000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_9945c8a3aa274e52aa7dfeabc6567ab4"
      unitRef="U002">34995000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_2aa6d352ef954e92b94b3e1d7fb0194a"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_e6854048f6c941b08d43417760c49b8d"
      unitRef="U002">818000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_d4953054b98b42dba9d5bed9a4393226"
      unitRef="U002">34177000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_2b2ee63d727e423482b317c18a37ce81"
      unitRef="U002">617692000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_22456af2bd1a42a5aaa84149b3a6373e"
      unitRef="U002">94000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_3f93907b739e4f8a80f71070bbbc98e2"
      unitRef="U002">15611000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_33930b14001f46ccb9bf26b44f06a253"
      unitRef="U002">602175000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_c63efe923e13426992c34154ca0ceb66"
      unitRef="U002">1567505000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_4d9475d7048b443985ccf0e54c482dde"
      unitRef="U002">227000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_abe680e773e045d898d7e780327a8001"
      unitRef="U002">19034000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FinancialInstrumentAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_ed64a9779a3842959199d38607dc68f6"
      unitRef="U002">1548698000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:EquitySecuritiesFvNiCost
      contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"
      decimals="-3"
      id="Fact_795298199a7149089987fd608d910788"
      unitRef="U002">11897000</us-gaap:EquitySecuritiesFvNiCost>
    <us-gaap:EquitySecuritiesFvNiUnrealizedGain
      contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"
      decimals="-3"
      id="Fact_95a1e63d6d4c49f48092f55cc7344a6f"
      unitRef="U002">3946000</us-gaap:EquitySecuritiesFvNiUnrealizedGain>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"
      decimals="-3"
      id="Fact_720e14f204184668ac412128829c1d4c"
      unitRef="U002">4274000</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"
      decimals="-3"
      id="Fact_c9668cdfca24444facba84f5586a8b21"
      unitRef="U002">11569000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNiCost
      contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"
      decimals="-3"
      id="Fact_642c9681829a411280b706605512aec4"
      unitRef="U002">23115000</us-gaap:EquitySecuritiesFvNiCost>
    <us-gaap:EquitySecuritiesFvNiUnrealizedGain
      contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"
      decimals="-3"
      id="Fact_5465f26f407f4c8cbf1a7f4bc78d58bb"
      unitRef="U002">16707000</us-gaap:EquitySecuritiesFvNiUnrealizedGain>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"
      decimals="-3"
      id="Fact_8f26e7f4482346919fb9fd971a0e1bd2"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"
      decimals="-3"
      id="Fact_c86ece7c238c409db75f4e86d57eaa03"
      unitRef="U002">39822000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNiCost
      contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesMember"
      decimals="-3"
      id="Fact_74700e6175be499286aad7c1da529560"
      unitRef="U002">35012000</us-gaap:EquitySecuritiesFvNiCost>
    <us-gaap:EquitySecuritiesFvNiUnrealizedGain
      contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesMember"
      decimals="-3"
      id="Fact_023010caa8f343509b0246de63732628"
      unitRef="U002">20653000</us-gaap:EquitySecuritiesFvNiUnrealizedGain>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20220101to20220331_FinancialInstrumentAxis_EquitySecuritiesMember"
      decimals="-3"
      id="Fact_b4350186c9724e47b1cac8c01c4216b9"
      unitRef="U002">4274000</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FinancialInstrumentAxis_EquitySecuritiesMember"
      decimals="-3"
      id="Fact_10dc545d20404abda7146b5a706c0e00"
      unitRef="U002">51391000</us-gaap:EquitySecuritiesFvNi>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost
      contextRef="c20220331"
      decimals="-3"
      id="Fact_6c45e37635ae4e82a8fe9a524ce7bc4f"
      unitRef="U002">1602517000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain
      contextRef="c20220331"
      decimals="-3"
      id="Fact_5ab4e59a3fb946b2bfa63a42fd6cc9c5"
      unitRef="U002">20880000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss
      contextRef="c20220331"
      decimals="-3"
      id="Fact_571cea17cf8743fbb59b7749cbf08cd2"
      unitRef="U002">23308000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi
      contextRef="c20220331"
      decimals="-3"
      id="Fact_29d056dd0bc546a5b95f13a73db1588f"
      unitRef="U002">1600089000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_b358568c049541b1856e64106205b629"
      unitRef="U002">383870000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_870aab605dd4403c879855738490612a"
      unitRef="U002">728000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_e219351c2ba44027b99a7eb94f4fb4bd"
      unitRef="U002">226000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_baf860337cb14231b2612b277c5a61c8"
      unitRef="U002">384372000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_68fdb285d5a54bedba4551932330f29f"
      unitRef="U002">48493000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_90dbffe642224d96bbf19226414d77d9"
      unitRef="U002">19000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_1777d6b10a6444f78df8d692409a590a"
      unitRef="U002">18000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_2130cf6d51914dc0afd1eccb0e4dfdad"
      unitRef="U002">48494000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_d8fc413c165c4a2c8aa4472257c08e29"
      unitRef="U002">45424000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_c7bb5d4884cd42d0a8a8ff87cdcd691a"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_32a3a41f82bb44c799d99e85af07437d"
      unitRef="U002">64000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_4ed162913c2d4a49b2bae214aa82a90e"
      unitRef="U002">45360000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_e6152f86899e46e196de685960cf0520"
      unitRef="U002">134770000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_976e0d2fac214a4a8ce8d68be3812eda"
      unitRef="U002">45000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_e332742abab244fa8bc1de590d821dcc"
      unitRef="U002">37000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_072984a5e1e94320b84fd889d20ca860"
      unitRef="U002">134778000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_5d62eb1de663460d8a9d559d81878a58"
      unitRef="U002">612557000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_32d0c20dd09a4965be6545f5ef1e1d0e"
      unitRef="U002">792000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_a65f661f76de418c8ded0d80f7684b50"
      unitRef="U002">345000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfOneYearOrLessMember"
      decimals="-3"
      id="Fact_5269f1e3ba9b4b5f9397e201edccca32"
      unitRef="U002">613004000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_a2fd30f9900b415194cd94d357af784b"
      unitRef="U002">382000000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_34ab02ad304f441abe8a81962651c7ce"
      unitRef="U002">331000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_3d4b4abb3a29485786b07cbc63b828cb"
      unitRef="U002">2644000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_e00dab3b4cb04062a2e6a17f853d0e52"
      unitRef="U002">379687000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_d714f0d4eecc4d92b9b830449bba7fd1"
      unitRef="U002">72935000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_270ced43418a4c2faa9a7f0a3bd756eb"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_cc8c6fd4825a4a8ca13fdce32ea0a599"
      unitRef="U002">561000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_11b446490081470aa73bc2871b0b1042"
      unitRef="U002">72374000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_e8d68ba6fad84cecafc9cdd32dea1e2f"
      unitRef="U002">137635000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_28fa2a9aa6c3425bb5c7af4315f2d4c3"
      unitRef="U002">139000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_feb5ebb376f64b648a49adafb20944f7"
      unitRef="U002">500000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_5a7c49cad6044951b9d764adb62179ca"
      unitRef="U002">137274000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_b4ec0071c45247e3b27a4b280e593780"
      unitRef="U002">39909000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_31520233cfb642e0bb7685bb15133f3a"
      unitRef="U002">1000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_81b005a6831247d6a900198d8738b3d0"
      unitRef="U002">224000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_e281a6848521414491c86fcd9f85c8a9"
      unitRef="U002">39686000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_8039b5caa1e74523933ab777edc0cc55"
      unitRef="U002">6136000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_ce80a712118d48bca2b5173f22d877be"
      unitRef="U002">0</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_7f14ae8a216045b6b0f1cba03a06d496"
      unitRef="U002">37000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_5191d04da6c34987a3faa2edb62ca0eb"
      unitRef="U002">6099000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_d8f9bd55d10c46e8a7923b828bf66f7b"
      unitRef="U002">638615000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_9edb30f88d124e4f98e5fc6733baa317"
      unitRef="U002">471000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_35b1772ea2884933bfa48eab5441097a"
      unitRef="U002">3966000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember_InvestmentSecondaryCategorizationAxis_SecuritiesWithMaturityOfMoreThanOneYearMember"
      decimals="-3"
      id="Fact_bd78e79378ff4eecb24ada86ee7d4685"
      unitRef="U002">635120000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_d8842e093daf4aa8a441e191da86ea99"
      unitRef="U002">1251172000</us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_4a16a27e0c4144fea9d33948c111d40b"
      unitRef="U002">1263000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax>
    <us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_5d60bf6074c241728013af9aebe4f553"
      unitRef="U002">4311000</us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FinancialInstrumentAxis_DebtSecuritiesMember"
      decimals="-3"
      id="Fact_282a1da5440143508a579978a45d2601"
      unitRef="U002">1248124000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:EquitySecuritiesFvNiCost
      contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"
      decimals="-3"
      id="Fact_b8a712e5f4af42cdb9018ff5937f5e79"
      unitRef="U002">11897000</us-gaap:EquitySecuritiesFvNiCost>
    <us-gaap:EquitySecuritiesFvNiUnrealizedGain
      contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"
      decimals="-3"
      id="Fact_8b35758c336d4c378e03fdeaeaa046d7"
      unitRef="U002">7145000</us-gaap:EquitySecuritiesFvNiUnrealizedGain>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"
      decimals="-3"
      id="Fact_d23a46f787e04e259237398f99054fea"
      unitRef="U002">837000</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember"
      decimals="-3"
      id="Fact_8651c4c7cf0b40ec9603b79cfd50d43b"
      unitRef="U002">18205000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNiCost
      contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"
      decimals="-3"
      id="Fact_2faff3973c0f4ab0bd4fcffd3307bce8"
      unitRef="U002">15615000</us-gaap:EquitySecuritiesFvNiCost>
    <us-gaap:EquitySecuritiesFvNiUnrealizedGain
      contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"
      decimals="-3"
      id="Fact_e3dee8ea479d4e8fbda5e68ba7814a7e"
      unitRef="U002">16707000</us-gaap:EquitySecuritiesFvNiUnrealizedGain>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"
      decimals="-3"
      id="Fact_53a829bbd230481e83c9e355f575a8b7"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember"
      decimals="-3"
      id="Fact_90b3f028c4c64df180eb902de39038aa"
      unitRef="U002">32322000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNiCost
      contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesMember"
      decimals="-3"
      id="Fact_cfbea931b88e4baf9112a7e54d02cbfc"
      unitRef="U002">27512000</us-gaap:EquitySecuritiesFvNiCost>
    <us-gaap:EquitySecuritiesFvNiUnrealizedGain
      contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesMember"
      decimals="-3"
      id="Fact_5e7e8a83411f4b40bf00d16a3e60d487"
      unitRef="U002">23852000</us-gaap:EquitySecuritiesFvNiUnrealizedGain>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20210101to20211231_FinancialInstrumentAxis_EquitySecuritiesMember"
      decimals="-3"
      id="Fact_d45ad7a12cac403ea2d5a2edb37a0eed"
      unitRef="U002">837000</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesMember"
      decimals="-3"
      id="Fact_8bd47c89fd1645cfa78adda562a9364e"
      unitRef="U002">50527000</us-gaap:EquitySecuritiesFvNi>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost
      contextRef="c20211231"
      decimals="-3"
      id="Fact_6808aa03681547cca1d6c98d32aab031"
      unitRef="U002">1278684000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain
      contextRef="c20211231"
      decimals="-3"
      id="Fact_f7a5c21d883b40c784a842b4eab86b9d"
      unitRef="U002">25115000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss
      contextRef="c20211231"
      decimals="-3"
      id="Fact_bf106be9d5824af3aa9e4c635557fb8a"
      unitRef="U002">5148000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss>
    <ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi
      contextRef="c20211231"
      decimals="-3"
      id="Fact_ecad1868d9ae4c4cb68ebd3c78a85d30"
      unitRef="U002">1298651000</ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi>
    <ions:NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets
      contextRef="c20220331"
      decimals="INF"
      id="Fact_602d828e78234435b39c13dda2bf144d"
      unitRef="U010">2</ions:NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20220101to20220331_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"
      decimals="-5"
      id="Fact_8c163df244e8495f8c0396f6ec856bf4"
      unitRef="U002">3400000</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:EquitySecuritiesFvNiUnrealizedLoss
      contextRef="c20220101to20220331_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"
      decimals="-5"
      id="Fact_cec1b18fe8e84d1ba09baf2edef0616b"
      unitRef="U002">3200000</us-gaap:EquitySecuritiesFvNiUnrealizedLoss>
    <us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock
      contextRef="c20220101to20220331"
      id="Text_f990914388cd4584984855ae82ba9a6b">
&lt;div style="display:none;"&gt;&lt;br/&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, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; (in thousands, except for number of investments). We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/span&gt;&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&lt;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;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Less than 12 Months of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;More than 12 Months of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Temporary&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impairment&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number of&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;337&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;647,390&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,694&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,300&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;658,690&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(12,041&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;95,543&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,697&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,685&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-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;(326&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105,228&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,023&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;44&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#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;406,747&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,539&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,860&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #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;(138&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;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;411,607&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,677&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;619&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-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;173,537&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,096&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;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,455&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;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;(98&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,992&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,194&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;1,315&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;(16&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,005&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: 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;(83&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;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;(99&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,017&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,324,532&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18,042&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;36,305&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(992&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,360,837&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;(19,034&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="0"
      id="Fact_333cdd7221c74a659058428cb96f027e"
      unitRef="U011">337</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_2e0cac4f3e6445e4af1d421cd8ba2264"
      unitRef="U002">647390000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_903a58d3bf3c421b9166ac1d0a37f22d"
      unitRef="U002">11694000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_183b7171ce6948fe93c1afb5708dc040"
      unitRef="U002">11300000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_2bc4f2d4d6bd455e9474ce6348458023"
      unitRef="U002">347000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_39ca68f5ced34e02a3fb7f209ed77346"
      unitRef="U002">658690000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_6a521c4aea4b4d6186a40cc4ac11ef16"
      unitRef="U002">12041000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="0"
      id="Fact_f82ef35b85bc4b76a2ca3ea408acca74"
      unitRef="U011">14</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_0a9f0760b76943a0bb457df5aa11d275"
      unitRef="U002">95543000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_a606df5dbef24526ade176d96aa0c07b"
      unitRef="U002">1697000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_2d0505e6d78b437083a13a36af9d0e35"
      unitRef="U002">9685000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_be6630f1d422413eb69c31e0abbb4c84"
      unitRef="U002">326000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_9e4b0d43d3f14d11b3cdc492ef07dd02"
      unitRef="U002">105228000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_eba3f72c498e466687adcba61f086b48"
      unitRef="U002">2023000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="0"
      id="Fact_2e46b5062fb3478c908336d6d2d994c6"
      unitRef="U011">44</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_392a47ad8b314b019fde0f086884f91a"
      unitRef="U002">406747000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_b473b5a2bf6f472895d5dbf195a86994"
      unitRef="U002">3539000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_631f14e2221f4205b5b6af1f14754c3c"
      unitRef="U002">4860000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_366adc85dd3e4261abd0ad4c81e9ed06"
      unitRef="U002">138000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_8fe8a8c8d9ba4dbe9a0815a2dd6c7215"
      unitRef="U002">411607000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_039c758638b24f77831d5dfe6f4ab76e"
      unitRef="U002">3677000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="0"
      id="Fact_2cef1dcb51a449edb7fe76af4b2c0e0c"
      unitRef="U011">619</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_2b2f7503adc14be999f6518218accc8a"
      unitRef="U002">173537000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_f999f2e853164a178503a3147b33ac68"
      unitRef="U002">1096000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_1ee53f584ab24cb6b581f7eae1eba196"
      unitRef="U002">5455000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_98453b0c0b144bba86ec994206fdc1cb"
      unitRef="U002">98000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_4d01726992bb4d94b31e50877ad828f0"
      unitRef="U002">178992000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_401d55f983434e8d9399ad8c2fc7758d"
      unitRef="U002">1194000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="0"
      id="Fact_a21f49784eae40489b0406c92c97e44e"
      unitRef="U011">3</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_ed6918e8de4a4cddb68b84b0973ef21c"
      unitRef="U002">1315000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_eb8bb8a7eb794fd2aa573bebbef50d6c"
      unitRef="U002">16000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_fe22a62f0cae44359a1087d8ba07f963"
      unitRef="U002">5005000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_e7162ed2803b4dcdb16f05d3cdc01bed"
      unitRef="U002">83000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_f5242826454a4306b595db9815050842"
      unitRef="U002">6320000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss
      contextRef="c20220331_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_378bb0ac33e34dfdbe5d8fb3bf1f7047"
      unitRef="U002">99000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions
      contextRef="c20220331"
      decimals="0"
      id="Fact_7e1f0b8e65b4437a89df6913266edd37"
      unitRef="U011">1017</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months
      contextRef="c20220331"
      decimals="-3"
      id="Fact_a321ec73c6744478ab33de1911123ebf"
      unitRef="U002">1324532000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss
      contextRef="c20220331"
      decimals="-3"
      id="Fact_32652639154d4153a0f3bf2d89e86160"
      unitRef="U002">18042000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger
      contextRef="c20220331"
      decimals="-3"
      id="Fact_c18b9c577f3c4038843a9b7ee496d0d4"
      unitRef="U002">36305000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss
      contextRef="c20220331"
      decimals="-3"
      id="Fact_b3760c7e65ef40e2ab47903dd7c9443a"
      unitRef="U002">992000</us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition
      contextRef="c20220331"
      decimals="-3"
      id="Fact_08acbc6cc04049ed9b3d48be01027292"
      unitRef="U002">1360837000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition>
    <us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss
      contextRef="c20220331"
      decimals="-3"
      id="Fact_cf642061255f4432b68bd3618eb2a416"
      unitRef="U002">19034000</us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss>
    <us-gaap:FairValueDisclosuresTextBlock
      contextRef="c20220101to20220331"
      id="Text_2a6de6f9bc2e421d838e9ff6c089fad5">
&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;The following tables present the major security types we held at March 31, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of March 31, 2022 and December 31, 2021, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;our Bicycle investment was subject to trading restrictions that extend to the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.&lt;/span&gt; The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;407,399&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;407,399&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;754,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;754,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (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;105,228&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;105,228&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;490,792&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;490,792&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (5)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;192,350&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;192,350&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (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;6,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;6,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in Bicycle Therapeutics plc (6)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,131&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,131&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in ProQR Therapeutics N.V. (6)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;438&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;438&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,967,666&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;898,629&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,057,906&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,131&lt;/div&gt;&lt;/td&gt;
    &lt;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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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, 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;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (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;764,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (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;120,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (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;182,634&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (7)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (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;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in Bicycle Therapeutics plc (6)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in ProQR Therapeutics N.V. (6)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,875&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;3,875&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,807,528&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;727,708&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,065,490&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/td&gt;
    &lt;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="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" style="font-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" style="font-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;$13.5 million was 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;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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" style="font-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;$15.0 million was 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;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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;$10.3 million was 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;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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" style="font-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;(7)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$2.3 million was 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;&lt;/div&gt;

&lt;div style="text-align: left; 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 0.125% Notes and 0% Notes had a fair value of $494.4 million and $595.4 million at March 31, 2022, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.&lt;/div&gt;
</us-gaap:FairValueDisclosuresTextBlock>
    <us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock
      contextRef="c20220101to20220331"
      id="Text_3fc22c693e28451987436214b4939105">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables present the major security types we held at March 31, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of March 31, 2022 and December 31, 2021, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;our Bicycle investment was subject to trading restrictions that extend to the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input.&lt;/span&gt; The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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, 2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;407,399&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;407,399&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;754,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;754,008&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (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;105,228&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;105,228&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (4)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;490,792&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;490,792&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (5)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;192,350&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-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;192,350&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (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;6,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;6,320&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in Bicycle Therapeutics plc (6)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,131&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,131&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in ProQR Therapeutics N.V. (6)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;438&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;438&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,967,666&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;898,629&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,057,906&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,131&lt;/div&gt;&lt;/td&gt;
    &lt;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&gt;&lt;br/&gt;&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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, 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;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (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;764,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (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;120,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (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;182,634&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (7)&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (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;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in Bicycle Therapeutics plc (6)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" valign="bottom"&gt;&lt;div&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Investment in ProQR Therapeutics N.V. (6)&lt;/div&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,875&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: 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;3,875&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,807,528&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;727,708&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,065,490&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;&lt;/td&gt;
    &lt;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="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" style="font-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" style="font-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;$13.5 million was 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;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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" style="font-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;$15.0 million was 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;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; 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;$10.3 million was 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;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;
  &lt;tr&gt;
    &lt;td style="width: 18pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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" style="font-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;(7)&lt;/td&gt;
    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$2.3 million was 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;
</us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_ab8b93d31763462f825afbb8d94ca1c5"
      unitRef="U002">407399000</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_435272b4ab6d4fb0a17848af08d9ea64"
      unitRef="U002">407399000</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_b9e898ee93984d899874de0b216f6350"
      unitRef="U002">0</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_ad9e4c4bff7e4a2395e4c4efbe25e180"
      unitRef="U002">0</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_1b769ef466ea447fba9ad51918866940"
      unitRef="U002">754008000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_1a622d10285342d4ab574fbc330e9b6a"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_2a11d5be65ff43b2bc3316d459599b2f"
      unitRef="U002">754008000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_ff48b2cde78e4246b9f8c0d3668f45a9"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_4ce9866198094ab9bb0fba527e9f7a46"
      unitRef="U002">105228000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_cc73c7dd4336416d8872098ddc72f3db"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_418e9f44ebbb42dd9a510d3d5c448b72"
      unitRef="U002">105228000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_63265628852a4ba29e93a651719977ed"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_144b8361be90457089523a487891e260"
      unitRef="U002">490792000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_80cb88c905824e2f9a4af8d421a3ae6c"
      unitRef="U002">490792000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_2e48b747b93e49a19ff9c8c29a110e0c"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_a2102c4b8ddf44179d1593de5f225b5c"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_c11eb07ea3324e24902d31be146e2aba"
      unitRef="U002">192350000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_5239338c06b14e6a85429a23967f6b00"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_d3641150e44941fa942aa4dc4b80dcba"
      unitRef="U002">192350000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_4256bb9f94cb424da59655cd85ab7f9f"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_5a3e302889e04832960498aaf3fc8b2b"
      unitRef="U002">6320000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_c79df577c73b4e58b8a6ebc687660780"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_0dfa9dad994240f3bfc133e3f1806e42"
      unitRef="U002">6320000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_d9283a639225417ab2226e23faf78f90"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"
      decimals="-3"
      id="Fact_063ea3aa6c0446b1901c679162b7098d"
      unitRef="U002">11131000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"
      decimals="-3"
      id="Fact_355b95f4be1a40aca92d8c591b590998"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"
      decimals="-3"
      id="Fact_588d4799502645ff9bb47bcf9ef264fc"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"
      decimals="-3"
      id="Fact_e2b3f77b6b2c4be3bafd76a92f2212c3"
      unitRef="U002">11131000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"
      decimals="-3"
      id="Fact_5715fb92aca2469f8d6b89bcc32dd2ad"
      unitRef="U002">438000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"
      decimals="-3"
      id="Fact_eaa3b06235c44c048a5d428f0fd68f15"
      unitRef="U002">438000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"
      decimals="-3"
      id="Fact_816cd8cab6a1437db6b65fcb66362f2b"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"
      decimals="-3"
      id="Fact_7130a91908584a7c9eff44721af2d068"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20220331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_9623b6fc811d446d8de6fe8c0a84d07a"
      unitRef="U002">1967666000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_5e3adc88dc374a21be5199cc974a06ca"
      unitRef="U002">898629000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_fb2ce086644c437499ac32ea8b2ab24d"
      unitRef="U002">1057906000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20220331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_7b5eb73a704b42f985034bdd93235dd2"
      unitRef="U002">11131000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_3abef904d1ac4dac9365cd6a89ce306b"
      unitRef="U002">541199000</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_d7eb290d8c5b4341953ea8ce19b70167"
      unitRef="U002">541199000</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_9d277c8fc4ff4a19a7ee29dcea9663b9"
      unitRef="U002">0</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:CashAndCashEquivalentsFairValueDisclosure
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_e0825e1067364ec09a168d5dbb04bd55"
      unitRef="U002">0</us-gaap:CashAndCashEquivalentsFairValueDisclosure>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_6d98cfd31fed4be1bc5dd4e5765ff970"
      unitRef="U002">764059000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_880b4c0e0d2d48df987d8eb4b3893eda"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_641d49c2d0c64af9adad977b14b03585"
      unitRef="U002">764059000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-3"
      id="Fact_0ccc9dc9ab324a0c8d69143093135087"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_a02ee28d048e4f4a86d13e676be48142"
      unitRef="U002">120868000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_2c0dd2ce365841a7940c2b161ab7aa5b"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_276eb2ce23b74c76b7109fee3b729859"
      unitRef="U002">120868000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-3"
      id="Fact_e9495bbff93745cdbd73aaf148a9dd4a"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_92f2c745baa2467ebc8da9f308582732"
      unitRef="U002">182634000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_4f65ddc8bb1f41b18f4a4fafb05aa5bf"
      unitRef="U002">182634000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_cad6d847f28b41d1ba345ee379c53c3a"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-3"
      id="Fact_a2deb395404a40e59f04a7af68529744"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_8ac6126992144e2d902abafe0f05aaf1"
      unitRef="U002">174464000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_c4b11390dafb4d68ab357a12be102e2b"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_984ae9d0003e4112b370b64ac08e73fa"
      unitRef="U002">174464000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-3"
      id="Fact_0602b31c9430474ba3e3239fa80848d7"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_3884240483e242908ec151549d8a9266"
      unitRef="U002">6099000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_a95b8a716a024353bd232c9287cc39cc"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_bee8ae5848674561afc84c3a3eeddfb7"
      unitRef="U002">6099000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember"
      decimals="-3"
      id="Fact_eda294b705b64b799f776b0e52f994d6"
      unitRef="U002">0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"
      decimals="-3"
      id="Fact_18bb66a7c7c8455bbd8d594108704256"
      unitRef="U002">14330000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"
      decimals="-3"
      id="Fact_4a150c4659c644349b579e7a6f26e609"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"
      decimals="-3"
      id="Fact_a3b9e5403eee4d9d87f1c1dfaf13ac3b"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_BicycleTherapeuticsPlcMember"
      decimals="-3"
      id="Fact_0f3b33ac1a704ec3b63b853cd5c2bef6"
      unitRef="U002">14330000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"
      decimals="-3"
      id="Fact_b0bdc20ef3184f16a0c2f40e12be4cfc"
      unitRef="U002">3875000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"
      decimals="-3"
      id="Fact_6a13d939e5dc429399070728b0932ea7"
      unitRef="U002">3875000</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"
      decimals="-3"
      id="Fact_44d66cda97bb4fbc8cdd4b7bef54d977"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:EquitySecuritiesFvNi
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_ProqrTherapeuticsNVMember"
      decimals="-3"
      id="Fact_236030e02f7644f8b79cdd10bd353619"
      unitRef="U002">0</us-gaap:EquitySecuritiesFvNi>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_d3bd323a8b614ca5970873ceac15876b"
      unitRef="U002">1807528000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_309c74f6dec14486a89fc6b78983b26a"
      unitRef="U002">727708000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_11ff54c661534a3abddbec83ad68c19a"
      unitRef="U002">1065490000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AssetsFairValueDisclosure
      contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember"
      decimals="-3"
      id="Fact_d6e03911cdb74cbaa033e42a7ae570af"
      unitRef="U002">14330000</us-gaap:AssetsFairValueDisclosure>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember"
      decimals="-5"
      id="Fact_f222017503d14900b7297dbf8ca32548"
      unitRef="U002">13500000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember"
      decimals="-5"
      id="Fact_23950cfc108a4c58977c3255b2c7769a"
      unitRef="U002">15000000.0</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20220331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember"
      decimals="-5"
      id="Fact_29824ec83f13463cb421396ade5c8f28"
      unitRef="U002">10300000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:AvailableForSaleSecuritiesDebtSecurities
      contextRef="c20211231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember"
      decimals="-5"
      id="Fact_08231978aefc42d3a9f2445f36d5a47c"
      unitRef="U002">2300000</us-gaap:AvailableForSaleSecuritiesDebtSecurities>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_dfc304a4577d4a8b8ccf97e7be8f9791"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_b605dc05faaa4ecf92f3388ccd8e6140"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:NotesPayableFairValueDisclosure
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member"
      decimals="-5"
      id="Fact_886896b6a5b643a387fb328dcc366ca9"
      unitRef="U002">494400000</us-gaap:NotesPayableFairValueDisclosure>
    <us-gaap:NotesPayableFairValueDisclosure
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member"
      decimals="-5"
      id="Fact_e2d5869342504cbea6cdb10162937afd"
      unitRef="U002">595400000</us-gaap:NotesPayableFairValueDisclosure>
    <us-gaap:IncomeTaxDisclosureTextBlock
      contextRef="c20220101to20220331"
      id="Text_5d168265bebe4eef9cbf660ffa2537c4">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;5.&#160; 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;Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over five years pursuant to Internal Revenue Code, or IRC, Section 174. Although the U.S. Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified. As a result, we recorded a $1.1 million income tax expense for the three months ended&#160;March 31, 2022 compared to $0.1 million income tax expense for the same period in 2021. &lt;/div&gt;
</us-gaap:IncomeTaxDisclosureTextBlock>
    <ions:AmortizationPeriodForResearchAndDevelopmentExpenditures
      contextRef="c20220101to20220331"
      id="Fact_2705398e97944d39b41b282331559e11">P5Y</ions:AmortizationPeriodForResearchAndDevelopmentExpenditures>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20220101to20220331"
      decimals="-5"
      id="Fact_1ddf6dc05f3447199bbd76650ac3a7b8"
      unitRef="U002">1100000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20210101to20210331"
      decimals="-5"
      id="Fact_d71da819015a406a9a7453adef2b9c98"
      unitRef="U002">100000</us-gaap:IncomeTaxExpenseBenefit>
    <us-gaap:CollaborativeArrangementDisclosureTextBlock
      contextRef="c20220101to20220331"
      id="Text_49a5ba0585764afaa86538e52aa60f04">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;6.&#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;2022&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, 2021&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 numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, Angelman Syndrome, 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, 2022, we have received $3.3 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, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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;40.1&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;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;/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: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;93.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;/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;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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;/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, 2022 and December 31, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;included deferred revenue of $385.5 million and $407.5 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 quarter of 2022, we did not have any material 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 the first quarter of 2022, we earned $18 million in milestone payments from Biogen when Biogen advanced two targets under our 2013 strategic collaboration. We recognized the milestone payments in full in the first quarter of 2022 because we did not have any remaining performance obligations related to the milestone payments. We will achieve the next payment of up to $10 million if Biogen advances a medicine under our 2013 strategic neurology collaboration.&lt;/div&gt;
</us-gaap:CollaborativeArrangementDisclosureTextBlock>
    <ions:CumulativePaymentsReceived
      contextRef="c20220331_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="-8"
      id="Fact_4de0101278b94f98a15dfb2c4990f91e"
      unitRef="U002">3300000000</ions:CumulativePaymentsReceived>
    <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock
      contextRef="c20220101to20220331"
      id="Text_eb04b7475c5c4dcca50d4367953aaa84">
&lt;div style="display:none;"&gt;&lt;br/&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, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

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

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;2022&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: left; text-indent: -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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;/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;40.1&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;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;/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: 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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;93.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&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;/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;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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-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;/tr&gt;
&lt;/table&gt;
</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_SpinrazaRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="-5"
      id="Fact_3bfe46d312174a25a4dfa7f2fa45dd19"
      unitRef="U002">53800000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_ProductOrServiceAxis_SpinrazaRoyaltiesMember_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="-5"
      id="Fact_24c482899718430ab80d1b8eea4f50c9"
      unitRef="U002">60000000.0</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="-5"
      id="Fact_7b42b2f36432432293763a6f77f80ea0"
      unitRef="U002">40100000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="-5"
      id="Fact_5bf8b26d53bb4758a6849a5a518e9d5e"
      unitRef="U002">18100000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="-5"
      id="Fact_6724abb5c13a4232947e36a5ec6e8a7f"
      unitRef="U002">93900000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20210331_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="-5"
      id="Fact_c129fb745a2941e19f25e008b752eba6"
      unitRef="U002">78100000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20220101to20220331_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="2"
      id="Fact_2378a184258a4c21b0f8a03a2ce4c8e8"
      unitRef="U003">0.66</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20210101to20210331_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="2"
      id="Fact_f9f72233c43a478a849fb1b7ab1a524e"
      unitRef="U003">0.70</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20220331_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="-5"
      id="Fact_5178e097d0c342cf84072f17ad124e39"
      unitRef="U002">385500000</us-gaap:ContractWithCustomerLiability>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20211231_TypeOfArrangementAxis_BiogenCollaborationsMember"
      decimals="-5"
      id="Fact_7b83a105f51e48c19c4fa834b14d4660"
      unitRef="U002">407500000</us-gaap:ContractWithCustomerLiability>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210401to20210630_ProductOrServiceAxis_Ion541Member_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember"
      decimals="-6"
      id="Fact_ab91654b7168476fa5495fb1d76b719d"
      unitRef="U002">18000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:NumberOfTargetsAdvanced
      contextRef="c20220101to20220331_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember"
      decimals="INF"
      id="Fact_92927dcd49a748aa867e72d5b5af4971"
      unitRef="U005">2</ions:NumberOfTargetsAdvanced>
    <ions:NextPotentialPayment
      contextRef="c20220331_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember"
      decimals="-6"
      id="Fact_11c23dc721af4581b81256e8aebe8b08"
      unitRef="U002">10000000</ions:NextPotentialPayment>
    <us-gaap:DebtDisclosureTextBlock
      contextRef="c20220101to20220331"
      id="Text_ef3a2cc101014877b712da5e56f03727">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;7. 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% Notes to repurchase $247.9 million in principal of our 1% Notes for $257.0 million.&lt;/div&gt;

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At March 31, 2022, 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.6&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; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde"&gt;April 2026&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our 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: 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, 2022, 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;548.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec"&gt;December 2024&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83.28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;123.38&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our 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;In April 2021, we repurchased $247.9 million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $8.6 million non-cash loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our 1% Notes. The non-cash loss on the early retirement of our debt is the difference between the amount paid to retire our 1% Notes and the net carrying balance of the liability at the time that we retired the debt. We paid the remaining principal balance of our 1% Notes with $62.0 million of cash at maturity in November 2021.&lt;/div&gt;

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

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

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

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; 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 &lt;/span&gt;100 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.&lt;/span&gt; The 1% Notes were subject to similar terms.&lt;/div&gt;
</us-gaap:DebtDisclosureTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_6084a279781c4f6f9d255000ab9021c3"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentFaceAmount
      contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="-5"
      id="Fact_31b7ba9c70ea47c98e3db30445a91628"
      unitRef="U002">632500000</us-gaap:DebtInstrumentFaceAmount>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_9dafbe4ac36f4acab7c5417e2b16fdb9"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentRepurchasedFaceAmount
      contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_367cca58a7ca4ff88703902e4e0bd9d7"
      unitRef="U002">247900000</us-gaap:DebtInstrumentRepurchasedFaceAmount>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_daaf05b5284740438b6e8f119ed98382"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:RepaymentsOfConvertibleDebt
      contextRef="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_b88be17da074442d8e0174eda1c066ff"
      unitRef="U002">257000000.0</us-gaap:RepaymentsOfConvertibleDebt>
    <us-gaap:ConvertibleDebtTableTextBlock
      contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      id="Text_7221b32ba4b8461895c3e851d9ac7ed7">
&lt;div style="display:none;"&gt;&lt;br/&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, 2022, 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12.6&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; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_109f9369bddf4793b7c1ba8f66869fde"&gt;April 2026&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;&lt;/div&gt;
</us-gaap:ConvertibleDebtTableTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_851b6e16263b47a8a5a3b794b32dee59"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_c94bff2160504f00b4aff81b982396f8"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentCarryingAmount
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="-5"
      id="Fact_edd5ff3b856642199ff86499cf0281a8"
      unitRef="U002">632500000</us-gaap:DebtInstrumentCarryingAmount>
    <us-gaap:DeferredFinanceCostsNet
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="-5"
      id="Fact_8ceb1a5736644a6b89bc5c24ba652acf"
      unitRef="U002">12600000</us-gaap:DeferredFinanceCostsNet>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_dce4bbae7b2a40908908ca4da1034984"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="3"
      id="Fact_e393d99c85b54051913a784296da3887"
      unitRef="U003">0.005</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:DebtInstrumentConvertibleConversionPrice1
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_b923c911082f4a9dbe578941ab6ba57e"
      unitRef="U004">57.84</us-gaap:DebtInstrumentConvertibleConversionPrice1>
    <ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_b9aacb5cbdd246a29518869cf1580bba"
      unitRef="U004">76.39</ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread>
    <ions:DebtInstrumentConvertibleSharesSubjectToConversion
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="-5"
      id="Fact_36af5452ef2d4158ba6f36e437b52979"
      unitRef="U001">10900000</ions:DebtInstrumentConvertibleSharesSubjectToConversion>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_a1c65db2db5e45bf9144abb23a3708cd"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_47594a78eeb74261b797d8f322986fa4"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_adfab887b13140eda35dd28df11ca681"
      unitRef="U004">76.39</ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_1e893f3eccd04fa886b5729d9095bb3a"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:CallSpread
      contextRef="c20210401to20210430"
      decimals="-5"
      id="Fact_9cea2f5d760e42c0a7580446a66d3538"
      unitRef="U002">46900000</ions:CallSpread>
    <us-gaap:PaymentsForHedgeFinancingActivities
      contextRef="c20210401to20210430"
      decimals="-5"
      id="Fact_36a469c4005348aa8141ff489585a08c"
      unitRef="U002">136700000</us-gaap:PaymentsForHedgeFinancingActivities>
    <us-gaap:ProceedsFromIssuanceOfWarrants
      contextRef="c20210401to20210430"
      decimals="-5"
      id="Fact_9dc32db714544a28860e525c4fab30e8"
      unitRef="U002">89800000</us-gaap:ProceedsFromIssuanceOfWarrants>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_327d187d871445adb18503b7c83d8bb1"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_1bb651c30fc64b0db83da188f8aae2f8"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_ca5f6c96b1124b2989fd762efdf51a1e"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_01da5b0bd9a8481f8816fdd4ee0aa0c5"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_7c0a89b92f644ec1a10cc74660014eab"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_76ff515a60454ce18e1a9984840953ae"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:ConvertibleDebtTableTextBlock
      contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      id="Text_4533b9a35aa54a2d981119b07e67d99c">
&lt;div style="display:none;"&gt;&lt;br/&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, 2022, 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" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&lt;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;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;548.8&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.0&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_c5b254d960d242d380e7e1f35dc8b7ec"&gt;December 2024&lt;/span&gt;&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83.28&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;123.38&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
  &lt;tr&gt;
    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;&lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;
    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;&lt;/td&gt;
    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;
  &lt;/tr&gt;
&lt;/table&gt;
</us-gaap:ConvertibleDebtTableTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_e999f0a79cc5454dbb35d79507c6bf14"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_9cc819b9413644d6b0245aee77431898"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentCarryingAmount
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-5"
      id="Fact_5b30f304e836422cb321c0bd36da9cea"
      unitRef="U002">548800000</us-gaap:DebtInstrumentCarryingAmount>
    <us-gaap:DeferredFinanceCostsNet
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-5"
      id="Fact_3f38f311c31c47e9afa1a4b179a0fa8a"
      unitRef="U002">6000000.0</us-gaap:DeferredFinanceCostsNet>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_f28004647502413bae9a04a5c327033e"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="3"
      id="Fact_a9ed75c8530a4cdd980eb1dc32b37ca0"
      unitRef="U003">0.005</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:DebtInstrumentConvertibleConversionPrice1
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="2"
      id="Fact_6424592d0e3847f9b21c7950d9891db7"
      unitRef="U004">83.28</us-gaap:DebtInstrumentConvertibleConversionPrice1>
    <ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="2"
      id="Fact_257883a038234987a42360f37188d9b5"
      unitRef="U004">123.38</ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread>
    <ions:DebtInstrumentConvertibleSharesSubjectToConversion
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-5"
      id="Fact_ed9c5d233d3b47b992cb88b28e7d96fe"
      unitRef="U001">6600000</ions:DebtInstrumentConvertibleSharesSubjectToConversion>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_fce48022202d43bb90824a8ab622ba1e"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_74c63dcb37a94b7c96fcda23934eccde"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_5e16fd8ed7c44c38864b21191b33ad87"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="2"
      id="Fact_706c33f17c1047e2b303834e2dfa9903"
      unitRef="U004">123.38</ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_8ada2275fc3149ba9239349b360d3ff0"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:CallSpread
      contextRef="c20191201to20191231"
      decimals="-5"
      id="Fact_376edf8306554bc9be15b3e5059f9689"
      unitRef="U002">52600000</ions:CallSpread>
    <us-gaap:PaymentsForHedgeFinancingActivities
      contextRef="c20191201to20191231"
      decimals="-5"
      id="Fact_63109fd55a644feaa1ceeef8ebde9e37"
      unitRef="U002">108700000</us-gaap:PaymentsForHedgeFinancingActivities>
    <us-gaap:ProceedsFromIssuanceOfWarrants
      contextRef="c20191201to20191231"
      decimals="-5"
      id="Fact_821561db37bf489ea047c585d83d7fb2"
      unitRef="U002">56100000</us-gaap:ProceedsFromIssuanceOfWarrants>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_8508261275f046e4bd44878636855c30"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_a599520206b24338ba155a460138e93b"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_9d674b898cb1469d9b4c18232244d3d9"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_dcf07dd5cb7a40b58bbb604e293f91c3"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_cf200a768fcb4dcb9dda4aaad67a8130"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_fd23717a1d4d4ec2ae3decc69589c581"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentRepurchasedFaceAmount
      contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_5733913e61d243aba64ac5cdde17967a"
      unitRef="U002">247900000</us-gaap:DebtInstrumentRepurchasedFaceAmount>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_7dce99cb33884aa695f60d9714cdbc63"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:GainsLossesOnExtinguishmentOfDebt
      contextRef="c20210401to20210630_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_475d555508dd44ec879d8264ff4f449f"
      unitRef="U002">8600000</us-gaap:GainsLossesOnExtinguishmentOfDebt>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_c7210172079a44a29a43562f67ccf9c3"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_a41d730fa97348cbb6f1560579771061"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_8adfad97b59c4a87a1edd27ef3c688bb"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:RepaymentsOfConvertibleDebt
      contextRef="c20211101to20211130_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_d0bfa204bf4c4321b5a5e9fcfe7261c1"
      unitRef="U002">62000000.0</us-gaap:RepaymentsOfConvertibleDebt>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_b2fc1c75f5c641f2b66eff5bf9e11829"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_c98e7aaf45cf42a78ac646beebca0a17"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange
      contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_537b73ba3c5546d3ac7077aac87f42f6"
      unitRef="U003">1</ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange>
    <ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange
      contextRef="c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="2"
      id="Fact_34a97d073e54403cb2f896dd5cda4e81"
      unitRef="U003">1</ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_be103130a6d84fa7b52179f2877f3f4e"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <link:footnoteLink
      xlink:role="http://www.xbrl.org/2003/role/link"
      xlink:type="extended">
        <link:loc
          xlink:href="#Fact_17f5c15fd8fe452b890ee866cfaa6b85"
          xlink:label="Fact_17f5c15fd8fe452b890ee866cfaa6b85"
          xlink:type="locator"/>
        <link:footnote id="Foot_2ec4116852e041e3a2a38cb16ff4ea22" xlink:label="Foot_2ec4116852e041e3a2a38cb16ff4ea22" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Includes investments classified as cash equivalents on our condensed consolidated balance sheet.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_17f5c15fd8fe452b890ee866cfaa6b85"
          xlink:to="Foot_2ec4116852e041e3a2a38cb16ff4ea22"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_7842515e18104a5cafcff84ddb01d951"
          xlink:label="Fact_7842515e18104a5cafcff84ddb01d951"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_7842515e18104a5cafcff84ddb01d951"
          xlink:to="Foot_2ec4116852e041e3a2a38cb16ff4ea22"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_d8fc413c165c4a2c8aa4472257c08e29"
          xlink:label="Fact_d8fc413c165c4a2c8aa4472257c08e29"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_d8fc413c165c4a2c8aa4472257c08e29"
          xlink:to="Foot_2ec4116852e041e3a2a38cb16ff4ea22"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_b358568c049541b1856e64106205b629"
          xlink:label="Fact_b358568c049541b1856e64106205b629"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_b358568c049541b1856e64106205b629"
          xlink:to="Foot_2ec4116852e041e3a2a38cb16ff4ea22"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_5a3e302889e04832960498aaf3fc8b2b"
          xlink:label="Fact_5a3e302889e04832960498aaf3fc8b2b"
          xlink:type="locator"/>
        <link:footnote id="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" xlink:label="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Included in short-term investments.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_5a3e302889e04832960498aaf3fc8b2b"
          xlink:to="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_6d98cfd31fed4be1bc5dd4e5765ff970"
          xlink:label="Fact_6d98cfd31fed4be1bc5dd4e5765ff970"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_6d98cfd31fed4be1bc5dd4e5765ff970"
          xlink:to="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_3884240483e242908ec151549d8a9266"
          xlink:label="Fact_3884240483e242908ec151549d8a9266"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_3884240483e242908ec151549d8a9266"
          xlink:to="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_4ce9866198094ab9bb0fba527e9f7a46"
          xlink:label="Fact_4ce9866198094ab9bb0fba527e9f7a46"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_4ce9866198094ab9bb0fba527e9f7a46"
          xlink:to="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_92f2c745baa2467ebc8da9f308582732"
          xlink:label="Fact_92f2c745baa2467ebc8da9f308582732"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_92f2c745baa2467ebc8da9f308582732"
          xlink:to="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_a02ee28d048e4f4a86d13e676be48142"
          xlink:label="Fact_a02ee28d048e4f4a86d13e676be48142"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_a02ee28d048e4f4a86d13e676be48142"
          xlink:to="Foot_67f6ff09f4d443248a7bd7fe03ce1bd9"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_1b769ef466ea447fba9ad51918866940"
          xlink:label="Fact_1b769ef466ea447fba9ad51918866940"
          xlink:type="locator"/>
        <link:footnote id="Foot_f8be77aa66f84482abc56f1b540c3aca" xlink:label="Foot_f8be77aa66f84482abc56f1b540c3aca" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$13.5 million was 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.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_1b769ef466ea447fba9ad51918866940"
          xlink:to="Foot_f8be77aa66f84482abc56f1b540c3aca"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_144b8361be90457089523a487891e260"
          xlink:label="Fact_144b8361be90457089523a487891e260"
          xlink:type="locator"/>
        <link:footnote id="Foot_f0cb78a83b31476988ccfd169edddb78" xlink:label="Foot_f0cb78a83b31476988ccfd169edddb78" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$15.0 million was 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.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_144b8361be90457089523a487891e260"
          xlink:to="Foot_f0cb78a83b31476988ccfd169edddb78"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_8ac6126992144e2d902abafe0f05aaf1"
          xlink:label="Fact_8ac6126992144e2d902abafe0f05aaf1"
          xlink:type="locator"/>
        <link:footnote id="Foot_5b9b3c8599d14902835320847fbc6b63" xlink:label="Foot_5b9b3c8599d14902835320847fbc6b63" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$2.3 million was 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.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_8ac6126992144e2d902abafe0f05aaf1"
          xlink:to="Foot_5b9b3c8599d14902835320847fbc6b63"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_c11eb07ea3324e24902d31be146e2aba"
          xlink:label="Fact_c11eb07ea3324e24902d31be146e2aba"
          xlink:type="locator"/>
        <link:footnote id="Foot_2009e9e101cd4940acd892bb1ca9a15f" xlink:label="Foot_2009e9e101cd4940acd892bb1ca9a15f" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">$10.3 million was 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.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_c11eb07ea3324e24902d31be146e2aba"
          xlink:to="Foot_2009e9e101cd4940acd892bb1ca9a15f"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_3abef904d1ac4dac9365cd6a89ce306b"
          xlink:label="Fact_3abef904d1ac4dac9365cd6a89ce306b"
          xlink:type="locator"/>
        <link:footnote id="Foot_a07f61350d6c43dcbc95f9a5735b974a" xlink:label="Foot_a07f61350d6c43dcbc95f9a5735b974a" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Included in cash and cash equivalents on our condensed consolidated balance sheet.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_3abef904d1ac4dac9365cd6a89ce306b"
          xlink:to="Foot_a07f61350d6c43dcbc95f9a5735b974a"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_ab8b93d31763462f825afbb8d94ca1c5"
          xlink:label="Fact_ab8b93d31763462f825afbb8d94ca1c5"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_ab8b93d31763462f825afbb8d94ca1c5"
          xlink:to="Foot_a07f61350d6c43dcbc95f9a5735b974a"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_063ea3aa6c0446b1901c679162b7098d"
          xlink:label="Fact_063ea3aa6c0446b1901c679162b7098d"
          xlink:type="locator"/>
        <link:footnote id="Foot_4aceaee590d24617870bb41115adebfe" xlink:label="Foot_4aceaee590d24617870bb41115adebfe" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Included in other current assets on our condensed consolidated balance sheet.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_063ea3aa6c0446b1901c679162b7098d"
          xlink:to="Foot_4aceaee590d24617870bb41115adebfe"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_18bb66a7c7c8455bbd8d594108704256"
          xlink:label="Fact_18bb66a7c7c8455bbd8d594108704256"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_18bb66a7c7c8455bbd8d594108704256"
          xlink:to="Foot_4aceaee590d24617870bb41115adebfe"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_5715fb92aca2469f8d6b89bcc32dd2ad"
          xlink:label="Fact_5715fb92aca2469f8d6b89bcc32dd2ad"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_5715fb92aca2469f8d6b89bcc32dd2ad"
          xlink:to="Foot_4aceaee590d24617870bb41115adebfe"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_b0bdc20ef3184f16a0c2f40e12be4cfc"
          xlink:label="Fact_b0bdc20ef3184f16a0c2f40e12be4cfc"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_b0bdc20ef3184f16a0c2f40e12be4cfc"
          xlink:to="Foot_4aceaee590d24617870bb41115adebfe"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_642c9681829a411280b706605512aec4"
          xlink:label="Fact_642c9681829a411280b706605512aec4"
          xlink:type="locator"/>
        <link:footnote id="Foot_55aad856d839435daad2d772a2ea1bc5" xlink:label="Foot_55aad856d839435daad2d772a2ea1bc5" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US"><xhtml:span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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</xhtml: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<xhtml:span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</xhtml:span></link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_642c9681829a411280b706605512aec4"
          xlink:to="Foot_55aad856d839435daad2d772a2ea1bc5"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_2faff3973c0f4ab0bd4fcffd3307bce8"
          xlink:label="Fact_2faff3973c0f4ab0bd4fcffd3307bce8"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_2faff3973c0f4ab0bd4fcffd3307bce8"
          xlink:to="Foot_55aad856d839435daad2d772a2ea1bc5"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_b8a712e5f4af42cdb9018ff5937f5e79"
          xlink:label="Fact_b8a712e5f4af42cdb9018ff5937f5e79"
          xlink:type="locator"/>
        <link:footnote id="Foot_20cf8a92586d4d88bc45b040cb662025" xlink:label="Foot_20cf8a92586d4d88bc45b040cb662025" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">Our equity securities included in other current assets consisted of our investments in two publicly traded companies, ProQR and Bicycle, which we classify as Level 1 and Level 3 investments, respectively. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2022, we recognized a $3.4 million and a $3.2 million unrealized loss on our condensed consolidated statement of operations related to our investments in ProQR and Bicycle, respectively. In the three months ended March 31, 2021, our equity securities included in other current assets only consisted of ProQR.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_b8a712e5f4af42cdb9018ff5937f5e79"
          xlink:to="Foot_20cf8a92586d4d88bc45b040cb662025"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_795298199a7149089987fd608d910788"
          xlink:label="Fact_795298199a7149089987fd608d910788"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_795298199a7149089987fd608d910788"
          xlink:to="Foot_20cf8a92586d4d88bc45b040cb662025"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_e3f0b01c2b014194af0169f71cb6cace"
          xlink:label="Fact_e3f0b01c2b014194af0169f71cb6cace"
          xlink:type="locator"/>
        <link:footnote id="Foot_74bbbb57209c4f53960b9d7c3438ee6b" xlink:label="Foot_74bbbb57209c4f53960b9d7c3438ee6b" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US">In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the three months ended March 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</link:footnote>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_e3f0b01c2b014194af0169f71cb6cace"
          xlink:to="Foot_74bbbb57209c4f53960b9d7c3438ee6b"
          xlink:type="arc"/>
        <link:loc
          xlink:href="#Fact_c25f6066e793481b89742397fce1babb"
          xlink:label="Fact_c25f6066e793481b89742397fce1babb"
          xlink:type="locator"/>
        <link:footnoteArc
          xlink:arcrole="http://www.xbrl.org/2003/arcrole/fact-footnote"
          xlink:from="Fact_c25f6066e793481b89742397fce1babb"
          xlink:to="Foot_74bbbb57209c4f53960b9d7c3438ee6b"
          xlink:type="arc"/>
    </link:footnoteLink>
</xbrl>
</XML>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EXCEL
<SEQUENCE>50
<FILENAME>Financial_Report.xlsx
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
begin 644 Financial_Report.xlsx
M4$L#!!0    ( &:)I%0'04UB@0   +$    0    9&]C4')O<',O87!P+GAM
M;$V./0L",1!$_\IQO;=!P4)B0-!2L+(/>QLOD&1#LD)^OCG!CVX>;QA&WPIG
M*N*I#BV&5(_C(I(/ !47BK9.7:=N')=HI6-Y #OGD<Z,STA)8*O4'J@)I9GF
M3?X.CD:?<@X>K7A.YNJQ<&4GPZ4A!0W_<FW>J=0U[R;UEA_6\#MI7E!+ P04
M    " !FB:142&$L"^X    K @  $0   &1O8U!R;W!S+V-O<F4N>&ULS9+!
M3L,P#(9?!>7>.LW8#E&7"X@32$A, G&+'&^+:-HH,6KW]K1EZX3@ 3C&_O/Y
ML^0:H\8NT7/J(B7VE&^&T+198]R*(W/4 !F/%&PNQT0[-O=="I;'9SI M/AA
M#P1*R@T$8NLL6YB 15R(PM0.-2:RW*4SWN&"CY^IF6$.@1H*U'*&JJQ F&EB
M/ U-#5? !&-*(7\7R"W$N?HG=NZ .">'[)=4W_=EOYISXPX5O#T]OLSK%K[-
M;%ND\5?VFD^1MN(R^75U=[][$$9)I0JY+N3M3E6ZDGJ]>9]<?_A=A4/G_-[_
M8^.+H*GAUUV8+U!+ P04    " !FB:14F5R<(Q &  "<)P  $P   'AL+W1H
M96UE+W1H96UE,2YX;6SM6EMSVC@4?N^OT'AG]FT+QC:!MK03<VEVV[29A.U.
M'X416(UL>621A'^_1S80RY8-[9)-NIL\!"SI^\Y%1^?H.'GS[BYBZ(:(E/)X
M8-DOV]:[MR_>X%<R)!%!,!FGK_# "J5,7K5::0##.'W)$Q+#W(*+"$MX%,O6
M7.!;&B\CUNJTV]U6A&ELH1A'9&!]7BQH0-!445IO7R"TY1\S^!7+5(UEHP$3
M5T$FN8BT\OELQ?S:WCYES^DZ'3*!;C ;6"!_SF^GY$Y:B.%4PL3 :F<_5FO'
MT=)(@(+)?90%NDGVH],5"#(-.SJ=6,YV?/;$[9^,RMIT-&T:X./Q>#BVR]*+
M<!P$X%&[GL*=]&R_I$$)M*-IT&38]MJND::JC5-/T_=]W^N;:)P*C5M/TVMW
MW=..B<:MT'@-OO%/A\.NB<:KT'3K:28G_:YKI.D6:$)&X^MZ$A6UY4#3( !8
M<';6S-(#EEXI^G64&MD=N]U!7/!8[CF)$?[&Q036:=(9EC1&<IV0!0X -\31
M3%!\KT&VBN#"DM)<D-;/*;50&@B:R('U1X(AQ=RO_?67N\FD,WJ=?3K.:Y1_
M::L!I^V[F\^3_'/HY)^GD]=-0LYPO"P)\?LC6V&')VX[$W(Z'&="?,_V]I&E
M)3+/[_D*ZTX\9Q]6EK!=S\_DGHQR([O=]EA]]D]';B/7J<"S(M>41B1%G\@M
MNN01.+5)#3(3/PB=AIAJ4!P"I DQEJ&&^+3&K!'@$WVWO@C(WXV(]ZMOFCU7
MH5A)VH3X$$8:XIQSYG/1;/L'I4;1]E6\W*.76!4!EQC?-*HU+,76>)7 \:V<
M/!T3$LV4"P9!AI<D)A*I.7Y-2!/^*Z7:_IS30/"4+R3Z2I&/:;,CIW0FS>@S
M&L%&KQMUAVC2/'K^!?F<-0H<D1L= F<;LT8AA&F[\!ZO)(Z:K<(1*T(^8ADV
M&G*U%H&V<:F$8%H2QM%X3M*T$?Q9K#63/F#([,V1=<[6D0X1DEXW0CYBSHN0
M$;\>ACA*FNVB<5@$_9Y>PTG!Z(++9OVX?H;5,VPLCO='U!=*Y \FIS_I,C0'
MHYI9";V$5FJ?JH<T/J@>,@H%\;D>/N5Z> HWEL:\4*Z">P'_T=HWPJOX@L Y
M?RY]SZ7ON?0]H=*W-R-]9\'3BUO>1FY;Q/NN,=K7-"XH8U=RS<C'5*^3*=@Y
MG\#L_6@^GO'M^MDDA*^:62TC%I!+@;-!)+C\B\KP*L0)Z&1;)0G+5--E-XH2
MGD(;;NE3]4J5U^6ON2BX/%ODZ:^A=#XLS_D\7^>TS0LS0[=R2^JVE+ZU)CA*
M]+',<$X>RPP[9SR2';9WH!TU^_9==N0CI3!3ET.X&D*^ VVZG=PZ.)Z8D;D*
MTU*0;\/YZ<5X&N(YV02Y?9A7;>?8T='[Y\%1L*/O/)8=QXCRHB'NH8:8S\-#
MAWE[7YAGE<90-!1M;*PD+$:W8+C7\2P4X&1@+: '@Z]1 O)256 Q6\8#*Y"B
M?$R,1>APYY=<7^/1DN/;IF6U;J\I=QEM(E(YPFF8$V>KRMYEL<%5'<]56_*P
MOFH]M!5.S_Y9K<B?#!%.%@L22&.4%Z9*HO,94[[G*TG$53B_13.V$I<8O./F
MQW%.4[@2=K8/ C*YNSFI>F4Q9Z;RWRT,"2Q;B%D2XDU=[=7GFYRN>B)V^I=W
MP6#R_7#)1P_E.^=?]%U#KG[VW>/Z;I,[2$R<><41 71% B.5' 86%S+D4.Z2
MD 83 <V4R43P H)DIAR F/H+O?(,N2D5SJT^.7]%+(.&3E[2)1(4BK ,!2$7
M<N/O[Y-J=XS7^BR!;814,F35%\I#B<$],W)#V%0E\Z[:)@N%V^)4S;L:OB9@
M2\-Z;ITM)__;7M0]M!<]1O.CF> >LX=SFWJXPD6L_UC6'ODRWSEPVSK> U[F
M$RQ#I'[!?8J*@!&K8KZZKT_Y)9P[M'OQ@2";_-;;I/;=X Q\U*M:I60K$3]+
M!WP?D@9CC%OT-%^/%&*MIK&MQMHQ#'F 6/,,H68XWX=%FAHSU8NL.8T*;T'5
M0.4_V]0-:/8--!R1!5XQF;8VH^1."CS<_N\-L,+$CN'MB[\!4$L#!!0    (
M &:)I%0SX0,8.P4  '45   8    >&PO=V]R:W-H965T<R]S:&5E=#$N>&UL
MI9A1<^(V$,>?KY]"P_2AG0FQ)4. &\(,(<F5Z5V.A/0ZUTX?A"W $]NBDAR2
M?OJNA+%)QJSI]"6QC??OGU>K_\H:;J5ZTFLA#'E)DTQ?MM;&;#YZG@[7(N7Z
M7&Y$!K\LI4JY@5.U\O1&"1ZYH#3QF.]?>"F/L]9HZ*[-U&@H<Y/$F9@IHO,T
MY>KU2B1R>]FBK?V%AWBU-O:"-QIN^$K,A?EM,U-PYI4J49R*3,<R(THL+UMC
M^G$2,!O@[O@6BZT^.";V5192/MF3:739\BV12$1HK 2'?\]B(I+$*@''WX5H
MJWRF#3P\WJO?NI>'EUEP+28R^3V.S/JRU6^12"QYGI@'N?U%%"_4M7JA3+3[
M2[:[>SN=%@ES;61:! -!&F>[__RE2,1!0. ?"6!% 'L70(\](2@" O>B.S+W
M6M?<\-%0R2U1]FY0LP<N-RX:WB;.[##.C8)?8X@SHVL9YC JAO L(C>9B<TK
MF6:[\K!I;A.]YDKHH6?@:3;&"POEJYTR.Z(<D"\R,VL-JI&(WL9[0%FBLCWJ
M%4,%OW!U3@)Z1IC/6 W/! \?;R"<]>O"W^ $9>8"IQ<<T9O(9Z'(G^.%-@J*
M\2]$LE-*=IQDIVDP'E\WHB[C>#CUV_<(1;>DZ*(R8T"(',9MPE=U&'C\DB=:
M(!P7)<?%:=FXS[DR0B6OY$%LI#)U2+B443E&U"N)>J<1S82*I9TO$8%95SM4
MN-*^EG_X\*&A'/LE6Q]5G.1*N3&+=<@3\EUPA?+A:NTV9>V (ER#DFMP6LX.
MP6[A8JVEX%H-J:)^97K^?X(JQO,H5H/</98H>F#%],3IKSCT2>>_QRN^0:QI
M%E)683%4J>@*MW$BR%V>+H2JQ<%%?-]OTP%E70RILEX:G(+T(%:Q=5](V1U/
M:\N\06@JLUB3&;2XE(<B-S%4@SZ##AB>8Z"5H5/<D@O0"8RJ@CJ;0BM\(;^*
MUUI47 HRZ/=['9^B*:Q,GN(N7?;Z4"HH,=?MS\C<@%T0J<A$YH ,Y#*JSRNN
M?GV#058=@.*^74 ^\A<RC2"'\1(&R,T+I!!QR2!H^T%P,>@%&&'5$2ANY 7A
M.(I@D0254QR0SW ?^9K5YPZ79/UNEWSB_\#25MAQ>#_]WY)6_8'BEOZ>=&+/
M8*0?Y3:KI6SH-UPE>L&QA1VM>@3%C?T]6UF&,R6?XRRL3R.N.1EC:\ZJ53#<
MV]^CS:0V,)/_B#='YT:#XH#YU,?8JH;!<(]W0SB&K[?C*+A [P(%J5H$P]W]
MLW1=="TSK$4TB P"VH;<H$15AV"XL3_&!F:/7!+*?EK\3.8BS!5DJQ8+5YK(
M- 7#F1L9/IV1'\]]GY(9K&&^\01=5+*J23#<V:'=1W&V(O/7="&36D1<8/KU
M;HZ15$V!X;:]3Q.Y>0G7/%N)HWVU0>AN/+\>8Q\CK.H![*0>L%_?[A9$+EU@
M$O7+M0;%[^\_9]^25=[/3O+^:08?)[OM"+O:YGO46C)<L8&L\GIVDM?;)1NT
M<O#2E53UM8_K?.8*:F <A@*$0";:26*,E>>SDSQ_GO(D(5>YAI]U_6CB.DT+
MW:"R^N DJ[])A5K9 OL$"F8-WIIN>%:;O@;!1K3*Z0/<J/?)6L.B  7Z?Q\%
M0>7XP4D?!6_-<>ZVBLC7W$"/S*RGU6W3%,I=IVRW&9]'M$-[@UZ_VQEZSX=8
MWL'&EAT5M]^G26@7I[L]KO)JN:<X=CMI7G7[;D,2OKAA4#5)Q!)"_?,>/%_M
M]OAV)T9NW#;90AHC4W>X%CP2RMX OR^E-/L3^X!RIW7T+U!+ P04    " !F
MB:14T>=GF8@&   W&@  &    'AL+W=O<FMS:&5E=',O<VAE970R+GAM;*V9
M;6_;-A#'OPIA%%@+.#$?]-@E 5(G0P.D:5"GVXMA+VB;L85*HB=22;-/OZ/L
M2(I(L2G0%VTD^TC]>3S>[TX^>935-[450J/O15ZJT\E6Z]W[V4RMMJ+@ZECN
M1 G?W,NJX!INJ\U,[2K!U\V@(I]1C*-9P;-R<G;2?'9;G9W(6N=9*6XKI.JB
MX-73!Y'+Q],)F3Q_\"7;;+7Y8'9VLN,;L1#ZZ^ZV@KM9.\LZ*T2I,EFB2MR?
M3L[)^SF+S8#&XL],/*K>-3)+64KYS=Q<K4\GV"@2N5AI,P6'/P]B+O+<S 0Z
M_CU,.FF?:0;VKY]G_Z-9/"QFR968R_RO;*VWIY-D@M;BGM>Y_B(?/XK#@D(S
MWTKFJOD?/1YL\02M:J5E<1@,"HJLW/_EWP^.Z T@P<@ >AA 7SN '0:P9J%[
M9<VR+KCF9R>5?$25L8;9S$7CFV8TK"8KS38N= 7?9C!.G\T_WUQ<WBPN+Q!<
M+3Y?7UV<W\'-A_/K\YOY)5I\O+R\6Z C]'5Q@=Z^>8?>H*Q$=UM9*UZNU<E,
M@P8STVQU>-Z'_?/HR/,^\>H8,3)%%%/J&#[W#[\0JW8X>3E\!BMOET_;Y=-F
M/C:V_+JJ1*D15TIH]=XS(VMG9,V,P=B,7&T1^ :MS(7XM\X>> Z/</IJ/U74
M3&4.W,-9&-"0L)/90]\GMED2I20EK=D+I4&K-/ J76QEI8^TJ K8TP>A=#$F
M<S]/V'L^"7&:)'B@TV%'@S!.J%MHV H-_2Z5I:[@O"O(&RL!_ESFPB4SM!Y/
M(T+I0*1M%9$DC=P2HU9BY)5X!0XLM:PRX71@9"L+,!LJ<UDE>$19W"J+O<H^
MZZVH()/TX]PE,7;M<1C' XT.LX"Q.'"+3%J1B5?DG=0\?X7(Q/80#1D$V4"E
MPXX%(0Y2M\RTE9EZ9=Y6@,]*/TW1+N=&*!QS<\)WYN1,42FT2W1JNRR.8TNS
MRPQV?T0RP5V"QW[17)MS/2KO,/R%LU*:A@-Y3C.,PQ%Y/?X0K[P+L9,J@[-M
MG"F;8!W?_\-<?1%ADO:V]:#589:&43RBM8,%H:\(4X\\:OLH)"E.AR?=91@1
M$J5X1&)''\)>!;0\X\LLSS0D)!_52 <+XJ?%^6HE:X@CM.-/8PF8.   &=@*
M)8<9>&DDAY .$\3/"9!8U0+(*PNH<A4W=:)3IHT $H6V3-N,)0D9VZ(.%<3/
MBF>9O2URJK1QD*8TC(8J;;,D":,QE1TVB)\;5R6X42#-OPO_GMM$2#$9BK2-
MV C72,<,XH?&<ZCOH(PQ'8&\1[DL-_N*1B[S;--$@-NY-B$"BBW?VE8LI&/"
M.XH0/T8<PJ'Q$/"AB=U]K0.E#E04M=OE-BI2H/ 0U2ZS."8CQXQV0*%^H+R$
M]0^BF#JP01-@\4"LRR[ 83@2Q[3C"_7SY;H-B9_R,;41PA@C+!GJ=MB%)(E'
ML$U[C8F?-=>N4)ZB7"C5^OX00$[]+A3%Q'*["T0L3D;4=QBB_BZH4U^ Q@W?
M"'#_TEE_'&9Z">L@&B+3:1;W6J672CNN43_7]M'\HRAV$"O!*6ST4*7+D*5I
M.*:S@QL-O6!?:+GZMI7Y6E3JMZ;JU$\^LM..1]3/H[DL"LA"RCQ@BM[@8XP)
M9/P*0>-:B]\1PWB*]_^0VO(*>,!K#<UC]I]83Q$)R#0.V10ZK::&,_>4@#D)
MG\TSI0SPF@JOUDK#159N$-?H$Z]6V_9] 'I;E[Q>9UJLWS76T.Z+8@DEX7/+
M/X4SJW:B>?>3/SFWRN8A":Q@<AF-M-.T0R;U(_-\#=+A/$(\[7BV/LI*M.*[
M#.++*=312J4)P[$54R[#*"!C]2SM"$K]!(5*I"[J'!J$Y]+;E$Z5V)K7= \"
M<*K<Q\'FXE&0A+9RAQVC43267CJ"4C]!^\(AK6>KS)U:; (>09B&.+*4NBQ)
MF*9XY."R#I?L-;A4CN/K?"-D<S"&1!,/NT6774QB-A(3K.,E\_/2RH?-07RU
M?!N'[@[(9>CK@%@'3N8')T:WHEH9/,YE^0#M>@:5*UJ(,I,5NI$:5O3WIR:K
M_.-[W==[W_=+.R[6D8GYR=27K_;R2R-_M)-G-GPB2"GI,-C==M""C;B^8Q3S
M-V#X&)J]7^/^CEXL^J7N[[(Y\V?SGW=_['J;FT3#FLMMQZS"?-9[JV]^4@%6
M;K)200EX#P/Q<0R;4>U_I=C?:+EK7O0OI=:R:"ZW@L.1-0;P_;T$_8<;\]M!
M^UO1V?]02P,$%     @ 9HFD5#V>NY<H P  - H  !@   !X;"]W;W)K<VAE
M971S+W-H965T,RYX;6RU5FMOTS 4_2M7$0B08'GT-::V4M<6K:)T92D@A/C@
M)K>--<<NMML"OQX[":&%+-T0]$-C._<<GW-O_.CNA;Q5":*&KRGCJN<D6F\N
M7%=%":9$G8D-<O-F)61*M.G*M:LV$DF<@5+F!I[7=E-"N=/O9F-SV>^*K6:4
MXUR"VJ8ID=\ND8E]S_&=GP,W=)UH.^#VNQNRQA#UN\U<FIY;LL0T1:ZHX"!Q
MU7,&_L70#RP@BWA/<:\.VF"M+(6XM9U)W',\JP@91MI2$//8X1 9LTQ&QY>"
MU"GGM,##]D_V5YEY8V9)% X%^T!CG?2<<P=B7)$MTS=B?X6%H9;EBP13V3_L
M\]AVQX%HJ[1("[!1D%*>/\G7(A$' +]Y!R H ,%] 8T"T,B,YLHR6R.B2;\K
MQ1ZDC39LMI'E)D,;-Y3;,H9:FK?4X'1_>#T;C6?A> 2F%5Y/)Z/!PG0N!]/!
M;#B&\&H\7H3P=$XD<IV@IA%AS^ %/ (75&)&5=?51H=E<Z-BSLM\SN"..=\0
M>08-_SD$7A!4P(?U\!%&)=P_AKO&?9F"H$Q!D/$U[N +M8AN$\%BE.H)X)<M
MU=\N:G@;)6\CXVW>E5J1IN9#59;^.6R(A!UA6X2GE$,L&"-2P09EGL9G56G,
M^3L9OUV/N[YWYGG&\^XP6Z>BCL0W2_'-!XC/*PUDJQ,AZ7>,,Q/Y:*7RG+QU
MH*GA%;_?U-\G\LA!JW30>K@#JM3VM/K6'YK\IM]I-7S[N1ZIKXP,?)/^5K7Z
M=JF^_7#U9AM6FO"8\O4I"^U[6ZB,K+/0*2UT:BUX,$<9F6T#AH+O4&JZ9 @A
M<BHDS(0VACZ]P72)\G/-:CLO9SNO7<73R>!R,ITL)N,0!K,1A(OKX>NKZ^EH
M?!,^@?';=Y/%QYII7I;3O*PU->$:3<XU2*(13(6B V\J]\:MMZJBU%/;5?NX
M:CM\,.S(F>_].@J\$TQ^T/HG1?,/CA__?Y;-_[7)^\'_*]P)[BQQE:7["V#N
MSSTXTNU]RIR9:\H5,%P9)N^L8Q:LS*\H>4>+37;*+X4V=X:LF9AK'4H;8-ZO
MA#%7=.S%H;PH]G\ 4$L#!!0    ( &:)I%3'* <H"08  .(9   8    >&PO
M=V]R:W-H965T<R]S:&5E=#0N>&ULI5G;;MLX$/T5PNA#"R2Q>-$M< PXMKOK
M16ZPTQ:[BWV0;=H6*HFN2"?IWR]UL:A(%)/6+[&DS(S.'))GAM3@F:7?^8Y2
M 5[B*.%7O9T0^\M^GZ]V- [X!=O31/YGP](X$/(VW?;Y/J7!.G>*HSZR+*<?
M!V'2&P[R9P_I<, .(@H3^I "?HCC(/UY32/V?-6#O>.#>;C=B>Q!?SC8!UNZ
MH.++_B&5=_TJRCJ,:<)#EH"4;JYZ(W@Y)CASR"V^AO29UZY!ELJ2L>_9S6Q]
MU;,R1#2B*Y&%".3/$QW3*,HB21P_RJ"]ZIV98_WZ&/USGKQ,9AEP.F;1MW M
M=E<]KP?6=!,<(C%GSW_2,B$[B[=B$<__@N?2UNJ!U8$+%I?.$D$<)L5O\%(2
M47.0<?0.J'1 30?2X8!+AYRY?H$L3VL2B& X2-DS2#-K&2V[R+G)O64V89(-
MXT*D\K^A]!/#\?W=9'JWF$Z O%K<W\PFHT=YLWB4/[?3N\<%N/\,[A^F\]'C
M3!J <_!E,0$?/WP"?!>DE(,P 8\[=N!!LN9GX,.K^T%?2(C9B_JK$LYU 0=U
MP,'@EB5BQ\$T6=/U:_^^3*W*#QWSNT;&@+=!>@$P/ /(0DB#9_Q^=VB @RNZ
M<1X/=\2;TR>:'.BE(12I0I$\%#&'TG%<.#JY8[:.GX:00!_Z@_Y3/76-&82.
MY59FKW#9%2[;F.+T14H,I]R4HU/%<HPYCAD7@&T #R*JG4V%NUU+@4#7:N39
M-D*VZ^FS="MD[AOL<QJDJ]V9U(PG*89[*6T"R$D/]H&0ESJP;@L'="!$3@.N
MQ@S[G@7U@+T*L&<$O)!*&2;;,["E"4V#*,<:K*6DA%RD02:F.LQ>"PPF$+D-
MR&TKF9COZQ'[%6+?B/B1"0E3%JP,7;(%M)Q8.IA^FS/?)P@W<+;-D(4[YP*T
ME(A:1J@WC'.P25E\A,L2O?A9+0#GMFM;I(%39R?7K]LQ!V!-[:%Q<=Z+'4VE
M1J]83,''DM%/IJ4*D8J-C"3,DB?*1;X.BA=H&4"ZD6J.D\:*. 1W9*_$%^(W
M$ HJ:Y8X3B4M0-RF'L&L=KQ&J#,CD'1 5*(.S:J>SR39WH05F?J)1-JO=QQD
M-U&VS:P.A$K>H6U$6)]"6FAV>X2]IF!HC+I&5]4*:"X6.75+*EM;>ISA(G@Q
MCG6[,IP[Q*HMLQ*MQL[S7=PA<% 5$6BN(K/WP6Q7A'-H^2W1T)GAKO%6=0.:
M"\>=W$M$DEHM,J_50IP[-G1:\U!CY_F>TT6@*A'07".N QZN0%)"!%)\B[X4
M?)1]Z)I%49#6GG[2YE"\P:MCLRY(LRKKS9R.!8]4Z4#FTC$)HX.@Z]-R*-_Q
M5@YZL\X<5%5!T-Q;%%N! Y=Y2,QR3N\/><E>FH:GV$#H\X%M#2'0]IL=K-;.
M<MV.28]4+4/F6M:9T=H\7*:<-)5/FY/.SI"3JG[(7/W&+(YIN@IE4U7N'<"_
MMS1>TO0_TT9+E2Y$3MW;(%5ED+G*&'8WI6==3%R$O*;F:,P\0DA'KX=4F4'F
M,K-XF-W-1_^,P)S]#"(1RFGR'AI534#NR30J\49F\3;1V&[:;>Q!KTFCQLR7
MTMU!HU)N]$9W/_UC,9W,\FW(M]'?-[.O\]%Q7IZ!K.B\@U6L9!9;I[**E=YA
ML]X96,5M17+DGKI!JL8*^A[NF)M8R18VR]9-N,I.V*1.9;06G5HQ37_^RIK'
MM>.,D\\SL!(0_-LG&KC=R$*$K69;J3$C#NJH;UB)$7Y+C(K-?L[JI+;?_Q5.
ME<!@YV1.E9K@M\XINCEM]XN.[^!F6ZDQ0ZZL6QVD*FG"9FD:9YW-DA5'#V"T
M32G]94Z5VF#_Y',WI27$W+*93M[:&W?BNUZ34XV9@5.BA(F8A6FZCUBVQ^4T
M 7^Q4++YF[.5*,DAZ&1FE9P0<XMB8A:W3RM]SVXJJ\:LV3CU:Z?ELB':YA\1
MN.SQ#HDH#I:KI]6'BE%^/-]X?@TOQ\7G!A6F^/IQ&Z3;,.$@HAL9TKIPY4BG
MQ0>%XD:P?7XFOV1"L#B_W-%@3=/,0/Y_PY@XWF0OJ#[K#/\'4$L#!!0    (
M &:)I%1<3X@"U0(  $T'   8    >&PO=V]R:W-H965T<R]S:&5E=#4N>&UL
MC97;;J,P$(9?Q4*]:*6V! BDK9)(.56-U!Q4TN[%:B\<<(*W8&=MD[3[]#LV
MA$TC$O4&//;\PS=C/&[ON'B7"2$*?60IDQTK46KS8-LR2DB&Y2W?$ 8K*RXR
MK, 4:UMN!,&Q$66I[38:@9UARJQNV\S-1;?-<Y521N8"R3S+L/CLDY3O.I9C
M[2=>Z#I1>L+NMC=X34*B7C=S 99=18EI1IBDG"%!5AVKYSP,6MK?.+Q1LI,'
M8Z0S67+^KHUQW+$:&HBD)%(Z H;7E@Q(FNI @/&GC&E5G]3"P_$^^J/)'7)9
M8DD&//U!8Y5TK#L+Q62%\U2]\-T3*?/Q=;R(I](\T:[T;5@HRJ7B62D&@HRR
MXHT_RCH<""!.O< M!>ZQH'E"X)4"SR1:D)FTAECA;EOP'1+:&Z+I@:F-44,V
ME.E=#)6 50HZU1W,IL/1-!P-$8S"V?-XV%N $2[@-1E-%R&:/<+29/XR>@*_
M\=L(/<_"$-V@UW"(+B^NT 6B#"T2GDO,8MFV%5#IV'94$O0+ O<$@8<FG*E$
MHA&+2?Q5;T,V54KN/J6^>S;@!(M;Y#G7R&VX;@W/X/MRYPR.5U78,_&\TQ7^
M7EW'4[!'Z%+7]PK]["VE$O"7_SK#T*P8FH:A>8)A"NT@Y;)V=PIE8)3ZS&^[
M-X'O!'[;WAX6K<;M[OXNN*_<OH#Y%9A_%NR50>M)Z5\2&SXB$1SMF"P5DB3*
M!564R&O$ )^OD,(?=0D47_ /R1R_Y0='"=2X>=#JZOF#BC\XRS_(A2 L^D2P
M54RFN&A-\6\XN-#J5!UN4(?;/(*M<W)/L+8JUM9Y5IY!HT]T!]Z2D[]#JV:?
MG4;K^'>H<;N'<CI'B/9!9\J(6)N&+5'$<Z:*$UW-5G="S[3"H_D^W!5%:_\?
MIKAHX+RN*9,H)2L(V;AM0=5$T;P+0_&-Z7]+KJ";FF$"]QT1V@'65YRKO:$_
M4-V@W7]02P,$%     @ 9HFD5,M,0S$^!@  $1X  !@   !X;"]W;W)K<VAE
M971S+W-H965T-BYX;6S-66UOVS80_BN$46 M4-<B]5XD!EK+0H.U21:G&X:B
M'Q29CH5*HBO1<;)?OY.L6A9)B5Z'%OT2B\YSQ^/#._(YZVS'BB_EFE*.'K,T
M+\]':\XWKR>3,E[3+"I?L0W-X3\K5F01AV%Q/RDW!8V6M5&63HAA.),L2O+1
M]*S^[KJ8GK$M3Y.<7A>HW&995#R]I2G;G8_PZ-L7-\G]FE=?3*9GF^B>+BC_
MN+DN8#0Y>%DF&<W+A.6HH*OST1O\.B1N95 C_DSHKCQZ1M52[AC[4@TNEN<C
MHXJ(IC3FE8L(/A[HC*9IY0GB^-HX'1WFK R/G[]Y#^O%PV+NHI+.6/I7LN3K
M\Y$W0DNZBK8IOV&[=[19D%WYBUE:UG_1KL$:(Q1O2\ZRQA@BR))\_QD]-D0<
M&1#28T : R(8F$Z/@=D8F(*!U6=@-0:6&)+?8V W!K9@@,T> Z<Q<&KN]V35
M3 <1CZ9G!=NAHD*#M^JAWJ[:&@A.\BJS%KR _R9@QZ>SJ\M@?KF8!PB>%E?O
M+X(WMS!8W,+'A_GE[0)=A3"ZFOW^[NI],+]9_(;F?WR\N/T;C=''18">/WN!
MRG54T!(E.;I=LVT9Y<OR)7K6&9]-. 1;33F)F\#>[@,C?8&Q+(/,6W 6?T&?
M/M#LCA:?%6YFPV[>+)=)E<)1BJZC9(DN<C2+-@F'\8#30.,TCK?9-HTX7:(K
MOJ8%@FBAL-=5Q3U0])Z5Y9#[^>GN [I*XH0/>0N'O=TR6&S7; ))<L@4<L@4
M4ONQ>OR\C=(HCRF*. 05OT(F?HF(00S5UNX].;6GZFQ[F&(+@ _'^Z; >+YM
M8[^+"V3<F&##Q5W87 '#V,2FX72!H0QT+9-XY #KL&,>V#%/8N<Y9/V^'EZ<
MQ-3>J]UERG0<=336(1JKMC-[HKG(8[AF2@@' JB?7E3E6!?3FJ5+6I10QU^W
M"7]"GVY8FB(XIG=1L?P\D"CV87)[D(I+N ]3J #5<FV)?#$M;(D0 1%H$7,9
M,?9\SQ$R*]3".LMW#LMW!I<_6T?Y/:WHWN9 ?9K\ V5<\4'A5,R!&[9"/'I4
ML>/H5C;3(@(9,38-L0CF6C^ASD^'&_? C3O(#6097/4Y7&Q%0?/X"?$BRDLX
MZ>"$5A'B:@G1(@(9,<9$Y$/K)M2XZ=#A'>CP!NFX*,MM?6I 2L3[^ZZL[SM(
MGICE>:.^=@E?(YIM4O9$:8/8P'&CK#!//E8%RCQI):YK>P)K,D@L,BTB5$[4
M4UW^@3+_AU)V?$"KZ/.EF#VC)V1LM!K+& RZ/G?'E0!>5D%#5U#6*8_H8_5,
ME>K(T!Z5#>0X6-/U'&&_ P5,W$L])-1.UN7F2'_B06ZNHR=H5'C9'(OUSE57
M5)+?E]"Z[%409^B!EAR^JV#"OD;5Q54BD)G )RWBI*0*%-M4C*N%*-93C17E
M;YNF*W(MXR2NM9!0/UN7[%;"X6$-]Y/)UA5;$VUGG<3N2ZE6BN'3M!CHKP]1
M<=!?6!F"J9"JXHF)%2K-)[9G2*4F \?$(H8IYH "APG!V+7%5)"1CF?8CM5#
M4JL0L?4]@E5/F*52K#[I"ZA5C7A8-O;T%^H@9!VIV#59WV'?L; C%:U"")K$
M<3QQUQ0XC&W?%_<W5"!=%[N]!=QJ2SPL+D]H,]2$R7(."(,^JB>@5M!A]^=W
M&K@54'A800WU&EB60M*QKA4Q@1XR5T#&CHT=J9:UN"X+K2;"PZ+H?[0<6!8\
M$DE:2*" P(7EVJ+,UKL*]:ZZOUZT(HP,B[#_VGL0K2::Z2&! @++L01>](Y"
MG:,N*ZW\(L/RZT>T($364^+93&2%@SU+;$(4*+'V])!0/5>/J"='/X<-:ZD?
MW8D061QY5L\%0EIM1(:UT?>T(D362%(ER#*%.,1TQ V58=*&:B&A=K(N-ZTD
M(L.2Z!=H19H(!ZF6!=C8!VTA4BW#)*JUD% [69?J5NR18;'WBS4B1*4 C;[#
MM55KY#2U)NAJH@S!44A:(NZ] N1[IN%*)Z<,'%N>+>+F*APT(K8ABM]0@70-
MWW;[2&H5)!G^3?"$1D1-F/R+'$A:UQ9S<W+T<JQZ60J.[Q-(B92NP-!XY8*'
M8O_^<3_@;%._+[MCG+.L?ES3")1L!8#_KQCCWP;5*[C#6^#IOU!+ P04
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M'2'%Z0Y6!F6B72,&_"TR'6$<R>X9/).]4Y/J9,F*THOVUJERTQA@W0.*&L!
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M,>."%'*R6JU8Y+M\-@]WEC_@S\I7K$1BJ()7 C8">(J</4:(BL^X%/N3'K1
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M/D7#<M>W6%Q$YQ5+P9N(HS'&]UZW^FA_O*K(Q]PEAW#"=:\KTDL#;R;R1\
M['<D9HI05D<\M](8G&O78";?NK^(<E=1R<^XJD^S%8";V!NPE0Z8MT"Y#1@C
MEX+">3NJ[D);"[Y=3,\4GG+9)XK3?%9E3YN3VK49]1N>'B9N1 Y@T+)1N$D_
M=. .[&\&E8NJ#@]L9EOC_?-,DR#&@3UT"CJUE7BH8_,!)K^\@;GU)U4L!]FY
M$D2 XS5&U.GX*BSH,<6V']!6+Z$&[YSU4E3&(LGKS8\4F0_?>%E%:;78KE(K
M.'M:ET1XE9$-85FZD10'V+%^CWF.BDS%DCIJ!X_-AZ"HAVLFZ7,TUPBET>.Z
M8P[MT/QE!L1BG5JYJ7VU8#X!/Q9\9FLXET:<DCQ8DZ[RR8LC#C )A'XNK&VD
MK1]+@"':N<"CKSF&5.!(H(,.[4!WOE)9<$ =-6L7WR#-'.C$&=&:CQZ3*YA:
MY7A8(K;(?P#-HEH#7P1UB!R.Y!$KN=_[:AU"Z'C2D?ILP\_6)2.97$FK@IY2
M0<=&%BG%N0^<%UNMT+R6 W>UD>.MCOE"/$PJ-9 8K3-T" FBL4,ZFL4>\32I
M$L>NP;P8<WG")1C.HR=CDTADS'2!X[]6"!J!D_X8L\J@@,>O2%9>/O##O2,@
M!X0V!1? H>[TECCQ@#,7I7J;(4F'A%)IC@Z% "XE:L1<C,L0/#-3/C[=U;?6
MB(;$P/'J3ZP]W(]R@4=TG[9QMB^(:*FP])2.3#I*? :D2.KAYK6;OKI>JG33
M4C$,AG1%L(#0].#P5=&#E&_UGR&%-E=&1K%%>9))$D?7JO#2=UV;95$GA0P=
M&N3KPU3])L"+.2+VT6:P254*@$0MAIQ+\D=%WCYHZ4N+B"U9YVS9^^(*\(%2
MIERK$Q1*!"@=$K JB3WG  9D#[4UARQO<C)I[?2H['4D._!)'QA,"K.GSF>Z
M)#C0<,X;JXSB2%VX&R+5/)1+9MD)XK"):BIOQ",I:F<*+B>JQ5-)XVTQ7Q;*
M!6_.S32UMQQ8SOA:$%\]-F%A482;5.6*O2)?C\NJP%61PBF5-<9/J/;'BVNT
M&'SAOHGKU'4HH4@0A$JM4;543:<V6AM5JE#-J<^SKPK=<L  *5/<DMR=%&NX
M"IT8XBF@/BX__QL9@Q=Y\*/UT7LE%DMT0\G;3O)*]C^P?]JRB\QN\1(BB!J,
M8$B)EZM!PI,4J]#+:"ZMA84M131:6G2)UPS9//PLXIAC/_R4Y=B *U-ROP;H
MV79#865N3*&LR5P=&5>RRZ4>F&6-\KQ!1.$1L2CEU"P6N[;D1LR)U(G%OD(K
MY;.%^E1E &H#[!/\JA5 OH&EL_?MNFB<;J#+ 5^\GO:U);[)ZD^R7]($M/4A
M\1O58L67QL8I^7QLN(ES@IFK=I3])B(<WMK2+( H8SYO JRFW#0?,A'C8%ST
M!90%;/6GFLK%\]X]628QB:F8Q< ?[6]6FGYIRHVX$71XF!MZ<W7R^L7)V^SR
M\U0.^[=Q<=U$?GRR &+LOY &2/.N@VB>FWLBUCB)].-+D4M!5I,DE9*4,;/[
M5%1S\MF0B?70HMA2N!N_?\[5B<G;^6M9<]7;KJ37:1#@V?7:5]DY@/#>*(!9
MM%*_Y@^ ZF2G([/'<]]D)/IZ-ALJ;L7U3 3,N@>YBA8/.*M->0@WQH+!0];+
M"5LW\\ ,/8Z]FLE\AP*A>&+G&X!VD,I"S.7LX1<>7PS*G;]<3$$X9\^% C$8
M8%N;^;0BV_?B'F@N48A&SN2\#>JWX=VE/-H]I;T?+NY_3=Y[KT+.NY!\=20%
MSD_/'CGS7)>I4&!95+&[@ZSH"IO-7$ZLJ7S&KD+^%24SXL8C$1\6(J,KM6F>
M5D]<+0PX#[&8&>R_-&"<MV!;'?)17(#"?6R@S!&"N[;FC?0H;FC%6(]=DU%L
M48[33N:VIPH&9Q'V=;43D67^'1R[HR(]04AVIFIB;X2&;$I$=X\2T40-[622
M2&I.HK/^*O*9<?%FZ@WLL.!@$G$+B;A(Y=UOTQ?J!TXDQP E$I76CE(=YLUS
M[B$./.5S1M6=$7U)"$^'FN!_7['JOU2C^M5R+Q3[/ C%/E$EY&R9CXRIT&ZY
MBW=R)LIYXCKM6-7B%EHLW[EZ!P[U5;^L!P00J;/DQQEWUJNQPF7P\<8E'D-1
M8X^50X VO9F6>X_'9\4Y9.2O?9$N"I[88:(,PQ_B#4\N;.DK3NMT<%KWSA;G
M_KP&2*(CNZB;0UULL8PHNES MAL6CD?/B*N?[OH*MKW2V=]4\^<!@SL7<'*5
M=U2C>U^O<37R_W%_DA8HMDH24G,>B-3@D*:AH$)\KSI8N%%=:8@5<^G]. 0?
MK X74"H<U$]NG?V ,7+Z<N)FP)TXA%#$P0/")CXF5#!SR')XX):N-96RN9UR
M8O7<KSZ_)-V@Y<37? $-E\H[<7]D1M<)PF%@9E=?O1^V08Y"F0^O[PT L7&9
M_.@:P WVYDHGDPC/#5'(SBF5/J5M.EAEN&JV<275%/[0B'$R1KS-:O'EDTZG
MV<<7]H:SA5L'2;E4 '1L) :*G3Z\ 0\<F2"<F<BN(7X&F[O!UI-CN\GV,2NZ
MJ^;+Q%92P2N7U^?BVTUZV_/@,F(2Q L6;>3X%UG9;WLQ(HKJ]]YV3*COW,WC
MXH@<S%VA3111&5,]W=+""]$@VWTL7>0HUVO(5][TB.^"<9%6<AD[R$1'V*&>
M?L"36ZQT QNZXA)CN67/#!7?^<6"](A)IC8A"RRI8\R2(LG$D[R@XA1&!Y8#
MSI+N(97M-Y+J(8X5;D]& ,91-K)XU=IT6G3P6I!"-_L<U9CE[]S&X>GTA#/7
M:J0.Q%?8<-F@=2E)L3$'2F,5:9-(2YAV<NEI3@+VV&KK_>W!IBE6<IPA^+*]
M"M5_TI+(CO++COW'=%5DZ];T.S*BP^);2G L419G96TL=\80"XA22%\NW1G1
M*3.CIZQ G-,FU%23DK-'XX8TZ&Q-43,1A_/,NI0MG\C=N."--:IOV6XZ%BY%
ME63*3U@O55)I=WR!J,VN/EPD;,%BVL%P8PYGNWI #VZ+<!+<S6(IS+5UOB/1
M=.P\'F$AU,^<UJ\/KIT(<H""(RA\U0G=)37,[2^B/#W:J-2I"9\L=0L25EJ%
MY1/YW["Q1%R0=K!DIPPSNU+Q[&E%RIU?[6H$L;6 S9?)*=%97^!I_A/<SK+
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M!#I-KZ\2H*$%#A-V;6P[>\?2Q.*PEJ\&4@B0_<HY/D_" 9?OT/H'4$L#!!0
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M'S_KD4\+>'H(KHY+[\P%K-#QML1_%O8B@.]SASVB>Q 'ZW]!YW\!4$L#!!0
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MCO#(,Z;2=0(::+IG*>S]8-\MJ]A)-)7&B"VH.IN*^3\\40)< ;85GL*Z/+B
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MK?53F9R7CLH(KQ(9$ZN,M$-&6% /HXO3"R*6%O$-!.V].:EA9N2;I)VBFF$
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M0K)R$:KLK/J*"FX!X&C9+EHVWIMG$OTTX!,5]\*FK!O2_Q@!B9>,H33M2TV
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MLGAR^.$<;SS6;@.^3Y6R]<09:%Z-%_\"4$L#!!0    ( &:)I%0'$9"MW0@
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M*B<\"B(\2YGX>Y?Q0(7^X@D*/QR13E[]N2$YAA>Z/4#?G@#I%-4&.14/S/A
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M:QPNZ-C5_:.@[UC5^HMXJRQ=Z[Y94UVHG0'-5XKV>>BX ./+;/T74$L#!!0
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M_4+5Q 8>Q*4V,F_ I"#GHOYGWYI"G "B20<@:@#1:T#8 1@T@,$KP* +,&P
M0U>9VHJKPYH9-I\J68&RT<1F'UPQ'9KL<V'7?6,4O>6$,_,-WPN^XS$3!A9Q
M+$MAN-C#H\QXS%%?PXKIM/Z%CU]+?F 9"J.!B03NQ0&UR=WX[1H-XYE^!U?
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MQ7-T2)%,M]J\V1K1P;L4RDZBVKGF-HYM7J-D=J ;5'12:B.9HZVI8ML89$4
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MEGBI 64WX'HAI=D-K(/NFC3]"U!+ P04    " !FB:14?>ONZ44,   !3
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M(KJ^:9%5S=_HL;6-3Z+IJJJ+15M8>;!(\_7_R5]M3^Q3 +8%8*\ Y)X"J"V
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M5&@MM8&Z?E<4]>:+OL'VU*^+_P-02P,$%     @ 9HFD5"EUQ*O\!0  8"0
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MG0?K*/^<O/Y&MV_D<'O3),J*O^!U*PO/P'2=Y<ERJ\QJL SCS?_@GVU+'**
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M=U',2U%,,B_!V8CCUB(I+/(9R,N5[=LVA!?#%U5=) >!#&%P1/LCP;H(&T1
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MW"=+A?FMRCJQH5-Q Q_;K-O:UA%. >N=PDG=@ MQ?\F6V9L/M\)Q'M17A'_
MGL&^(KP ]GON*WZ=5"VG:2IE"3]AZ:E> TL5C+LL6],9F/P 7P>/ _ I83/
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M.)O>R4P)A">V0P.7<[2,E^8*/L+S8@Z7%U=P 5S"4Z%JPV1N1J&EH X:9FV
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MNNGX<?G81 GG(\X6;L9WOU!+ P04    " !FB:148]:*%)L!  "4%P  $P
M %M#;VYT96YT7U1Y<&5S72YX;6S-F,UNPC 0A%\ERA418[NE/P(N;:\MA[Z
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M              "  <P!  !X;"]T:&5M92]T:&5M93$N>&UL4$L! A0#%
M  @ 9HFD5#/A Q@[!0  =14  !@              ("!#0@  'AL+W=O<FMS
M:&5E=',O<VAE970Q+GAM;%!+ 0(4 Q0    ( &:)I%31YV>9B 8  #<:   8
M              " @7X-  !X;"]W;W)K<VAE971S+W-H965T,BYX;6Q02P$"
M% ,4    " !FB:14/9Z[ER@#   T"@  &               @($\%   >&PO
M=V]R:W-H965T<R]S:&5E=#,N>&UL4$L! A0#%     @ 9HFD5,<H!R@)!@
MXAD  !@              ("!FA<  'AL+W=O<FMS:&5E=',O<VAE970T+GAM
M;%!+ 0(4 Q0    ( &:)I%1<3X@"U0(  $T'   8              " @=D=
M  !X;"]W;W)K<VAE971S+W-H965T-2YX;6Q02P$"% ,4    " !FB:14RTQ#
M,3X&   1'@  &               @('D(   >&PO=V]R:W-H965T<R]S:&5E
M=#8N>&UL4$L! A0#%     @ 9HFD5#8Q7$F@!P  +Q\  !@
M ("!6"<  'AL+W=O<FMS:&5E=',O<VAE970W+GAM;%!+ 0(4 Q0    ( &:)
MI%23!WVGP@,  .D(   8              " @2XO  !X;"]W;W)K<VAE971S
M+W-H965T."YX;6Q02P$"% ,4    " !FB:14L3;XSG(G   ZA0  &
M        @($F,P  >&PO=V]R:W-H965T<R]S:&5E=#DN>&UL4$L! A0#%
M  @ 9HFD5'J6BXCH"0  K!P  !D              ("!SEH  'AL+W=O<FMS
M:&5E=',O<VAE970Q,"YX;6Q02P$"% ,4    " !FB:14#$MG.TX'  "(%@
M&0              @('M9   >&PO=V]R:W-H965T<R]S:&5E=#$Q+GAM;%!+
M 0(4 Q0    ( &:)I%0H;[<Y'0,  ),&   9              " @7)L  !X
M;"]W;W)K<VAE971S+W-H965T,3(N>&UL4$L! A0#%     @ 9HFD5"^2FP9I
M!0  $0T  !D              ("!QF\  'AL+W=O<FMS:&5E=',O<VAE970Q
M,RYX;6Q02P$"% ,4    " !FB:14=%)F!9('  ".%P  &0
M@(%F=0  >&PO=V]R:W-H965T<R]S:&5E=#$T+GAM;%!+ 0(4 Q0    ( &:)
MI%12Z?.7V ,  %P)   9              " @2]]  !X;"]W;W)K<VAE971S
M+W-H965T,34N>&UL4$L! A0#%     @ 9HFD5)7(^[Y,-0  <[T  !D
M         ("!/H$  'AL+W=O<FMS:&5E=',O<VAE970Q-BYX;6Q02P$"% ,4
M    " !FB:14K542([T%  !!#@  &0              @('!M@  >&PO=V]R
M:W-H965T<R]S:&5E=#$W+GAM;%!+ 0(4 Q0    ( &:)I%0'$9"MW0@  &L:
M   9              " @;6\  !X;"]W;W)K<VAE971S+W-H965T,3@N>&UL
M4$L! A0#%     @ 9HFD5**P:WI!!0  QA   !D              ("!R<4
M 'AL+W=O<FMS:&5E=',O<VAE970Q.2YX;6Q02P$"% ,4    " !FB:14B,2(
M5,,"   K!@  &0              @(%!RP  >&PO=V]R:W-H965T<R]S:&5E
M=#(P+GAM;%!+ 0(4 Q0    ( &:)I%3V:[4%:@,  *4)   9
M  " @3O.  !X;"]W;W)K<VAE971S+W-H965T,C$N>&UL4$L! A0#%     @
M9HFD5*WOELQ*!0  Y14  !D              ("!W-$  'AL+W=O<FMS:&5E
M=',O<VAE970R,BYX;6Q02P$"% ,4    " !FB:140,YS==,"   R"   &0
M            @(%=UP  >&PO=V]R:W-H965T<R]S:&5E=#(S+GAM;%!+ 0(4
M Q0    ( &:)I%003*?O60(  %(%   9              " @6?:  !X;"]W
M;W)K<VAE971S+W-H965T,C0N>&UL4$L! A0#%     @ 9HFD5%.;I#U0 P
M]0D  !D              ("!]]P  'AL+W=O<FMS:&5E=',O<VAE970R-2YX
M;6Q02P$"% ,4    " !FB:14U:U$4MT"  #_"   &0              @(%^
MX   >&PO=V]R:W-H965T<R]S:&5E=#(V+GAM;%!+ 0(4 Q0    ( &:)I%2Y
MZJ'-6@(  "D%   9              " @9+C  !X;"]W;W)K<VAE971S+W-H
M965T,C<N>&UL4$L! A0#%     @ 9HFD5&J"ZB@' P  %@L  !D
M     ("!(^8  'AL+W=O<FMS:&5E=',O<VAE970R."YX;6Q02P$"% ,4
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M+GAM;%!+ 0(4 Q0    ( &:)I%1]Z^[I10P   %,   9              "
M@43[  !X;"]W;W)K<VAE971S+W-H965T,S,N>&UL4$L! A0#%     @ 9HFD
M5"EUQ*O\!0  8"0  !D              ("!P <! 'AL+W=O<FMS:&5E=',O
M<VAE970S-"YX;6Q02P$"% ,4    " !FB:14B8Z6X0H+  !65P  &0
M        @('S#0$ >&PO=V]R:W-H965T<R]S:&5E=#,U+GAM;%!+ 0(4 Q0
M   ( &:)I%3KMP8>:@(  ,<%   9              " @309 0!X;"]W;W)K
M<VAE971S+W-H965T,S8N>&UL4$L! A0#%     @ 9HFD5"DEU,^-!   =A4
M !D              ("!U1L! 'AL+W=O<FMS:&5E=',O<VAE970S-RYX;6Q0
M2P$"% ,4    " !FB:1478$.OJD%   4&@  &0              @(&9( $
M>&PO=V]R:W-H965T<R]S:&5E=#,X+GAM;%!+ 0(4 Q0    ( &:)I%2[ @ ,
M(0,  &@2   -              "  7DF 0!X;"]S='EL97,N>&UL4$L! A0#
M%     @ 9HFD5)>*NQS     $P(   L              ( !Q2D! %]R96QS
M+RYR96QS4$L! A0#%     @ 9HFD5-QW0:YI P  Z!D   \
M ( !KBH! 'AL+W=O<FMB;V]K+GAM;%!+ 0(4 Q0    ( &:)I%2WO<)+@0$
M "D7   :              "  40N 0!X;"]?<F5L<R]W;W)K8F]O:RYX;6PN
M<F5L<U!+ 0(4 Q0    ( &:)I%1CUHH4FP$  )07   3              "
M ?TO 0!;0V]N=&5N=%]4>7!E<UTN>&UL4$L%!@     N "X >0P  ,DQ 0
!  $!

end
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>51
<FILENAME>Show.js
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
// Edgar(tm) Renderer was created by staff of the U.S. Securities and Exchange Commission.  Data and content created by government employees within the scope of their employment are not subject to domestic copyright protection. 17 U.S.C. 105.
var Show={};Show.LastAR=null,Show.showAR=function(a,r,w){if(Show.LastAR)Show.hideAR();var e=a;while(e&&e.nodeName!='TABLE')e=e.nextSibling;if(!e||e.nodeName!='TABLE'){var ref=((window)?w.document:document).getElementById(r);if(ref){e=ref.cloneNode(!0);
e.removeAttribute('id');a.parentNode.appendChild(e)}}
if(e)e.style.display='block';Show.LastAR=e};Show.hideAR=function(){Show.LastAR.style.display='none'};Show.toggleNext=function(a){var e=a;while(e.nodeName!='DIV')e=e.nextSibling;if(!e.style){}else if(!e.style.display){}else{var d,p_;if(e.style.display=='none'){d='block';p='-'}else{d='none';p='+'}
e.style.display=d;if(a.textContent){a.textContent=p+a.textContent.substring(1)}else{a.innerText=p+a.innerText.substring(1)}}}
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>52
<FILENAME>report.css
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
/* Updated 2009-11-04 */
/* v2.2.0.24 */

/* DefRef Styles */
..report table.authRefData{
	background-color: #def;
	border: 2px solid #2F4497;
	font-size: 1em;
	position: absolute;
}

..report table.authRefData a {
	display: block;
	font-weight: bold;
}

..report table.authRefData p {
	margin-top: 0px;
}

..report table.authRefData .hide {
	background-color: #2F4497;
	padding: 1px 3px 0px 0px;
	text-align: right;
}

..report table.authRefData .hide a:hover {
	background-color: #2F4497;
}

..report table.authRefData .body {
	height: 150px;
	overflow: auto;
	width: 400px;
}

..report table.authRefData table{
	font-size: 1em;
}

/* Report Styles */
..pl a, .pl a:visited {
	color: black;
	text-decoration: none;
}

/* table */
..report {
	background-color: white;
	border: 2px solid #acf;
	clear: both;
	color: black;
	font: normal 8pt Helvetica, Arial, san-serif;
	margin-bottom: 2em;
}

..report hr {
	border: 1px solid #acf;
}

/* Top labels */
..report th {
	background-color: #acf;
	color: black;
	font-weight: bold;
	text-align: center;
}

..report th.void	{
	background-color: transparent;
	color: #000000;
	font: bold 10pt Helvetica, Arial, san-serif;
	text-align: left;
}

..report .pl {
	text-align: left;
	vertical-align: top;
	white-space: normal;
	width: 200px;
	white-space: normal; /* word-wrap: break-word; */
}

..report td.pl a.a {
	cursor: pointer;
	display: block;
	width: 200px;
	overflow: hidden;
}

..report td.pl div.a {
	width: 200px;
}

..report td.pl a:hover {
	background-color: #ffc;
}

/* Header rows... */
..report tr.rh {
	background-color: #acf;
	color: black;
	font-weight: bold;
}

/* Calendars... */
..report .rc {
	background-color: #f0f0f0;
}

/* Even rows... */
..report .re, .report .reu {
	background-color: #def;
}

..report .reu td {
	border-bottom: 1px solid black;
}

/* Odd rows... */
..report .ro, .report .rou {
	background-color: white;
}

..report .rou td {
	border-bottom: 1px solid black;
}

..report .rou table td, .report .reu table td {
	border-bottom: 0px solid black;
}

/* styles for footnote marker */
..report .fn {
	white-space: nowrap;
}

/* styles for numeric types */
..report .num, .report .nump {
	text-align: right;
	white-space: nowrap;
}

..report .nump {
	padding-left: 2em;
}

..report .nump {
	padding: 0px 0.4em 0px 2em;
}

/* styles for text types */
..report .text {
	text-align: left;
	white-space: normal;
}

..report .text .big {
	margin-bottom: 1em;
	width: 17em;
}

..report .text .more {
	display: none;
}

..report .text .note {
	font-style: italic;
	font-weight: bold;
}

..report .text .small {
	width: 10em;
}

..report sup {
	font-style: italic;
}

..report .outerFootnotes {
	font-size: 1em;
}
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>53
<FILENAME>FilingSummary.xml
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<XML>
<?xml version='1.0' encoding='utf-8'?>
<FilingSummary>
  <Version>3.22.1</Version>
  <ProcessingTime/>
  <ReportFormat>html</ReportFormat>
  <ContextCount>236</ContextCount>
  <ElementCount>246</ElementCount>
  <EntityCount>1</EntityCount>
  <FootnotesReported>true</FootnotesReported>
  <SegmentCount>69</SegmentCount>
  <ScenarioCount>0</ScenarioCount>
  <TuplesReported>false</TuplesReported>
  <UnitCount>13</UnitCount>
  <MyReports>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R1.htm</HtmlFileName>
      <LongName>000100 - Document - Document and Entity Information</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/DocumentAndEntityInformation</Role>
      <ShortName>Document and Entity Information</ShortName>
      <MenuCategory>Cover</MenuCategory>
      <Position>1</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R2.htm</HtmlFileName>
      <LongName>010000 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/CondensedConsolidatedBalanceSheets</Role>
      <ShortName>CONDENSED CONSOLIDATED BALANCE SHEETS</ShortName>
      <MenuCategory>Statements</MenuCategory>
      <Position>2</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R3.htm</HtmlFileName>
      <LongName>010100 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical</Role>
      <ShortName>CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical)</ShortName>
      <MenuCategory>Statements</MenuCategory>
      <Position>3</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R4.htm</HtmlFileName>
      <LongName>020000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations</Role>
      <ShortName>CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS</ShortName>
      <MenuCategory>Statements</MenuCategory>
      <Position>4</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R5.htm</HtmlFileName>
      <LongName>030000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss</Role>
      <ShortName>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS</ShortName>
      <MenuCategory>Statements</MenuCategory>
      <Position>5</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R6.htm</HtmlFileName>
      <LongName>040000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity</Role>
      <ShortName>CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY</ShortName>
      <MenuCategory>Statements</MenuCategory>
      <Position>6</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R7.htm</HtmlFileName>
      <LongName>050000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows</Role>
      <ShortName>CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS</ShortName>
      <MenuCategory>Statements</MenuCategory>
      <Position>7</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R8.htm</HtmlFileName>
      <LongName>060100 - Disclosure - Basis of Presentation</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/BasisOfPresentation</Role>
      <ShortName>Basis of Presentation</ShortName>
      <MenuCategory>Notes</MenuCategory>
      <Position>8</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R9.htm</HtmlFileName>
      <LongName>060200 - Disclosure - Significant Accounting Policies</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPolicies</Role>
      <ShortName>Significant Accounting Policies</ShortName>
      <MenuCategory>Notes</MenuCategory>
      <Position>9</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R10.htm</HtmlFileName>
      <LongName>060300 - Disclosure - Investments</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/Investments</Role>
      <ShortName>Investments</ShortName>
      <MenuCategory>Notes</MenuCategory>
      <Position>10</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R11.htm</HtmlFileName>
      <LongName>060400 - Disclosure - Fair Value Measurements</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/FairValueMeasurements</Role>
      <ShortName>Fair Value Measurements</ShortName>
      <MenuCategory>Notes</MenuCategory>
      <Position>11</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R12.htm</HtmlFileName>
      <LongName>060500 - Disclosure - Income Taxes</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/IncomeTaxes</Role>
      <ShortName>Income Taxes</ShortName>
      <MenuCategory>Notes</MenuCategory>
      <Position>12</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R13.htm</HtmlFileName>
      <LongName>060600 - Disclosure - Collaborative Arrangements and Licensing Agreements</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreements</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements</ShortName>
      <MenuCategory>Notes</MenuCategory>
      <Position>13</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R14.htm</HtmlFileName>
      <LongName>060700 - Disclosure - Convertible Debt</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/ConvertibleDebt</Role>
      <ShortName>Convertible Debt</ShortName>
      <MenuCategory>Notes</MenuCategory>
      <Position>14</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R15.htm</HtmlFileName>
      <LongName>070100 - Disclosure - Basis of Presentation (Policies)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/BasisOfPresentationPolicies</Role>
      <ShortName>Basis of Presentation (Policies)</ShortName>
      <MenuCategory>Policies</MenuCategory>
      <ParentRole>http://ionispharma.com/role/SignificantAccountingPolicies</ParentRole>
      <Position>15</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R16.htm</HtmlFileName>
      <LongName>070200 - Disclosure - Significant Accounting Policies (Policies)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesPolicies</Role>
      <ShortName>Significant Accounting Policies (Policies)</ShortName>
      <MenuCategory>Policies</MenuCategory>
      <ParentRole>http://ionispharma.com/role/SignificantAccountingPolicies</ParentRole>
      <Position>16</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R17.htm</HtmlFileName>
      <LongName>080200 - Disclosure - Significant Accounting Policies (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesTables</Role>
      <ShortName>Significant Accounting Policies (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://ionispharma.com/role/SignificantAccountingPolicies</ParentRole>
      <Position>17</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R18.htm</HtmlFileName>
      <LongName>080300 - Disclosure - Investments (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/InvestmentsTables</Role>
      <ShortName>Investments (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://ionispharma.com/role/Investments</ParentRole>
      <Position>18</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R19.htm</HtmlFileName>
      <LongName>080400 - Disclosure - Fair Value Measurements (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/FairValueMeasurementsTables</Role>
      <ShortName>Fair Value Measurements (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://ionispharma.com/role/FairValueMeasurements</ParentRole>
      <Position>19</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R20.htm</HtmlFileName>
      <LongName>080600 - Disclosure - Collaborative Arrangements and Licensing Agreements (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsTables</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreements</ParentRole>
      <Position>20</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R21.htm</HtmlFileName>
      <LongName>080700 - Disclosure - Convertible Debt (Tables)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/ConvertibleDebtTables</Role>
      <ShortName>Convertible Debt (Tables)</ShortName>
      <MenuCategory>Tables</MenuCategory>
      <ParentRole>http://ionispharma.com/role/ConvertibleDebt</ParentRole>
      <Position>21</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R22.htm</HtmlFileName>
      <LongName>090200 - Disclosure - Significant Accounting Policies, Revenue Recognition (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails</Role>
      <ShortName>Significant Accounting Policies, Revenue Recognition (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>22</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R23.htm</HtmlFileName>
      <LongName>090202 - Disclosure - Significant Accounting Policies, Contracts Receivable (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails</Role>
      <ShortName>Significant Accounting Policies, Contracts Receivable (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>23</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R24.htm</HtmlFileName>
      <LongName>090204 - Disclosure - Significant Accounting Policies, Deferred Revenue (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesDeferredRevenueDetails</Role>
      <ShortName>Significant Accounting Policies, Deferred Revenue (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>24</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R25.htm</HtmlFileName>
      <LongName>090208 - Disclosure - Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails</Role>
      <ShortName>Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>25</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R26.htm</HtmlFileName>
      <LongName>090210 - Disclosure - Significant Accounting Policies, Inventory Valuation (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails</Role>
      <ShortName>Significant Accounting Policies, Inventory Valuation (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>26</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R27.htm</HtmlFileName>
      <LongName>090212 - Disclosure - Significant Accounting Policies, Leases (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails</Role>
      <ShortName>Significant Accounting Policies, Leases (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>27</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R28.htm</HtmlFileName>
      <LongName>090214 - Disclosure - Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails</Role>
      <ShortName>Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>28</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R29.htm</HtmlFileName>
      <LongName>090216 - Disclosure - Significant Accounting Policies, Convertible Debt (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails</Role>
      <ShortName>Significant Accounting Policies, Convertible Debt (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>29</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R30.htm</HtmlFileName>
      <LongName>090218 - Disclosure - Significant Accounting Policies, Segment Information (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesSegmentInformationDetails</Role>
      <ShortName>Significant Accounting Policies, Segment Information (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>30</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R31.htm</HtmlFileName>
      <LongName>090220 - Disclosure - Significant Accounting Policies, Stock-Based Compensation Expense (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails</Role>
      <ShortName>Significant Accounting Policies, Stock-Based Compensation Expense (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>31</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R32.htm</HtmlFileName>
      <LongName>090300 - Disclosure - Investments, Contract Maturity of Available-for-Sale Securities (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails</Role>
      <ShortName>Investments, Contract Maturity of Available-for-Sale Securities (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>32</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R33.htm</HtmlFileName>
      <LongName>090302 - Disclosure - Investments, Summary of Investments (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails</Role>
      <ShortName>Investments, Summary of Investments (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>33</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R34.htm</HtmlFileName>
      <LongName>090304 - Disclosure - Investments, Investments Temporarily Impaired (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails</Role>
      <ShortName>Investments, Investments Temporarily Impaired (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <Position>34</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R35.htm</HtmlFileName>
      <LongName>090400 - Disclosure - Fair Value Measurements (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/FairValueMeasurementsDetails</Role>
      <ShortName>Fair Value Measurements (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://ionispharma.com/role/FairValueMeasurementsTables</ParentRole>
      <Position>35</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R36.htm</HtmlFileName>
      <LongName>090500 - Disclosure - Income Taxes (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/IncomeTaxesDetails</Role>
      <ShortName>Income Taxes (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://ionispharma.com/role/IncomeTaxes</ParentRole>
      <Position>36</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R37.htm</HtmlFileName>
      <LongName>090600 - Disclosure - Collaborative Arrangements and Licensing Agreements (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails</Role>
      <ShortName>Collaborative Arrangements and Licensing Agreements (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsTables</ParentRole>
      <Position>37</Position>
    </Report>
    <Report instance="form10q.htm">
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <HtmlFileName>R38.htm</HtmlFileName>
      <LongName>090700 - Disclosure - Convertible Debt (Details)</LongName>
      <ReportType>Sheet</ReportType>
      <Role>http://ionispharma.com/role/ConvertibleDebtDetails</Role>
      <ShortName>Convertible Debt (Details)</ShortName>
      <MenuCategory>Details</MenuCategory>
      <ParentRole>http://ionispharma.com/role/ConvertibleDebtTables</ParentRole>
      <Position>38</Position>
    </Report>
    <Report>
      <IsDefault>false</IsDefault>
      <HasEmbeddedReports>false</HasEmbeddedReports>
      <LongName>All Reports</LongName>
      <ReportType>Book</ReportType>
      <ShortName>All Reports</ShortName>
    </Report>
  </MyReports>
  <InputFiles>
    <File doctype="10-Q" original="form10q.htm">form10q.htm</File>
    <File>ex10-1.htm</File>
    <File>ex31_1.htm</File>
    <File>ex31_2.htm</File>
    <File>ex32_1.htm</File>
    <File>ions-20220331.xsd</File>
    <File>ions-20220331_cal.xml</File>
    <File>ions-20220331_def.xml</File>
    <File>ions-20220331_lab.xml</File>
    <File>ions-20220331_pre.xml</File>
  </InputFiles>
  <SupplementalFiles/>
  <BaseTaxonomies>
    <BaseTaxonomy items="714">http://fasb.org/us-gaap/2021-01-31</BaseTaxonomy>
    <BaseTaxonomy items="29">http://xbrl.sec.gov/dei/2021q4</BaseTaxonomy>
  </BaseTaxonomies>
  <HasPresentationLinkbase>true</HasPresentationLinkbase>
  <HasCalculationLinkbase>true</HasCalculationLinkbase>
</FilingSummary>
</XML>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>JSON
<SEQUENCE>56
<FILENAME>MetaLinks.json
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
{
 "instance": {
  "form10q.htm": {
   "axisCustom": 0,
   "axisStandard": 20,
   "contextCount": 236,
   "dts": {
    "calculationLink": {
     "local": [
      "ions-20220331_cal.xml"
     ]
    },
    "definitionLink": {
     "local": [
      "ions-20220331_def.xml"
     ]
    },
    "inline": {
     "local": [
      "form10q.htm"
     ]
    },
    "labelLink": {
     "local": [
      "ions-20220331_lab.xml"
     ]
    },
    "presentationLink": {
     "local": [
      "ions-20220331_pre.xml"
     ]
    },
    "schema": {
     "local": [
      "ions-20220331.xsd"
     ],
     "remote": [
      "http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd",
      "http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd",
      "http://www.xbrl.org/2003/xl-2003-12-31.xsd",
      "http://www.xbrl.org/2003/xlink-2003-12-31.xsd",
      "http://www.xbrl.org/2004/ref-2004-08-10.xsd",
      "http://www.xbrl.org/2005/xbrldt-2005.xsd",
      "http://www.xbrl.org/2006/ref-2006-02-27.xsd",
      "http://www.xbrl.org/lrr/arcrole/factExplanatory-2009-12-16.xsd",
      "http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd",
      "http://www.xbrl.org/lrr/role/net-2009-12-16.xsd",
      "http://www.xbrl.org/lrr/role/reference-2009-12-16.xsd",
      "https://www.xbrl.org/2020/extensible-enumerations-2.0.xsd",
      "https://www.xbrl.org/dtr/type/2020-01-21/types.xsd",
      "https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd",
      "https://xbrl.fasb.org/srt/2021/elts/srt-roles-2021-01-31.xsd",
      "https://xbrl.fasb.org/srt/2021/elts/srt-types-2021-01-31.xsd",
      "https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd",
      "https://xbrl.fasb.org/us-gaap/2021/elts/us-roles-2021-01-31.xsd",
      "https://xbrl.fasb.org/us-gaap/2021/elts/us-types-2021-01-31.xsd",
      "https://xbrl.sec.gov/country/2021/country-2021.xsd",
      "https://xbrl.sec.gov/currency/2021/currency-2021.xsd",
      "https://xbrl.sec.gov/dei/2021q4/dei-2021q4.xsd",
      "https://xbrl.sec.gov/exch/2021/exch-2021.xsd",
      "https://xbrl.sec.gov/naics/2021/naics-2021.xsd",
      "https://xbrl.sec.gov/sic/2021/sic-2021.xsd",
      "https://xbrl.sec.gov/stpr/2021/stpr-2021.xsd"
     ]
    }
   },
   "elementCount": 435,
   "entityCount": 1,
   "hidden": {
    "http://fasb.org/us-gaap/2021-01-31": 6,
    "http://ionispharma.com/20220331": 2,
    "http://xbrl.sec.gov/dei/2021q4": 5,
    "total": 13
   },
   "keyCustom": 41,
   "keyStandard": 205,
   "memberCustom": 34,
   "memberStandard": 35,
   "nsprefix": "ions",
   "nsuri": "http://ionispharma.com/20220331",
   "report": {
    "R1": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "dei:DocumentType",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "document",
     "isDefault": "true",
     "longName": "000100 - Document - Document and Entity Information",
     "role": "http://ionispharma.com/role/DocumentAndEntityInformation",
     "shortName": "Document and Entity Information",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "dei:DocumentType",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R10": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:InvestmentTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060300 - Disclosure - Investments",
     "role": "http://ionispharma.com/role/Investments",
     "shortName": "Investments",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:InvestmentTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R11": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:FairValueDisclosuresTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060400 - Disclosure - Fair Value Measurements",
     "role": "http://ionispharma.com/role/FairValueMeasurements",
     "shortName": "Fair Value Measurements",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:FairValueDisclosuresTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R12": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:IncomeTaxDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060500 - Disclosure - Income Taxes",
     "role": "http://ionispharma.com/role/IncomeTaxes",
     "shortName": "Income Taxes",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:IncomeTaxDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R13": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:CollaborativeArrangementDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060600 - Disclosure - Collaborative Arrangements and Licensing Agreements",
     "role": "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreements",
     "shortName": "Collaborative Arrangements and Licensing Agreements",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:CollaborativeArrangementDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R14": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:DebtDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060700 - Disclosure - Convertible Debt",
     "role": "http://ionispharma.com/role/ConvertibleDebt",
     "shortName": "Convertible Debt",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:DebtDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R15": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:BasisOfAccountingPolicyPolicyTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "070100 - Disclosure - Basis of Presentation (Policies)",
     "role": "http://ionispharma.com/role/BasisOfPresentationPolicies",
     "shortName": "Basis of Presentation (Policies)",
     "subGroupType": "policies",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:BasisOfAccountingPolicyPolicyTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R16": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:RevenueFromContractWithCustomerPolicyTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "070200 - Disclosure - Significant Accounting Policies (Policies)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies",
     "shortName": "Significant Accounting Policies (Policies)",
     "subGroupType": "policies",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:RevenueFromContractWithCustomerPolicyTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R17": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:ScheduleOfInventoryCurrentTableTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "080200 - Disclosure - Significant Accounting Policies (Tables)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesTables",
     "shortName": "Significant Accounting Policies (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:ScheduleOfInventoryCurrentTableTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R18": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "080300 - Disclosure - Investments (Tables)",
     "role": "http://ionispharma.com/role/InvestmentsTables",
     "shortName": "Investments (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R19": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "080400 - Disclosure - Fair Value Measurements (Tables)",
     "role": "http://ionispharma.com/role/FairValueMeasurementsTables",
     "shortName": "Fair Value Measurements (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R2": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:CashAndCashEquivalentsAtCarryingValue",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "statement",
     "isDefault": "false",
     "longName": "010000 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS",
     "role": "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
     "shortName": "CONDENSED CONSOLIDATED BALANCE SHEETS",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:CashAndCashEquivalentsAtCarryingValue",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R20": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "080600 - Disclosure - Collaborative Arrangements and Licensing Agreements (Tables)",
     "role": "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsTables",
     "shortName": "Collaborative Arrangements and Licensing Agreements (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R21": {
     "firstAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:ConvertibleDebtTableTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "080700 - Disclosure - Convertible Debt (Tables)",
     "role": "http://ionispharma.com/role/ConvertibleDebtTables",
     "shortName": "Convertible Debt (Tables)",
     "subGroupType": "tables",
     "uniqueAnchor": {
      "ancestors": [
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:ConvertibleDebtTableTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R22": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090200 - Disclosure - Significant Accounting Policies, Revenue Recognition (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails",
     "shortName": "Significant Accounting Policies, Revenue Recognition (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20180401to20180630_MajorCustomersAxis_BiogenIncMember",
      "decimals": "INF",
      "lang": null,
      "name": "ions:NumberOfAgreementsWithCollaborationPartner",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U006",
      "xsiNil": "false"
     }
    },
    "R23": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "ions:NumberOfSignificantCustomers",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U009",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090202 - Disclosure - Significant Accounting Policies, Contracts Receivable (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails",
     "shortName": "Significant Accounting Policies, Contracts Receivable (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "ions:NumberOfSignificantCustomers",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U009",
      "xsiNil": "false"
     }
    },
    "R24": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-5",
      "first": true,
      "lang": null,
      "name": "us-gaap:ContractWithCustomerLiabilityRevenueRecognized",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090204 - Disclosure - Significant Accounting Policies, Deferred Revenue (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesDeferredRevenueDetails",
     "shortName": "Significant Accounting Policies, Deferred Revenue (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-5",
      "first": true,
      "lang": null,
      "name": "us-gaap:ContractWithCustomerLiabilityRevenueRecognized",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R25": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment",
      "reportCount": 1,
      "unitRef": "U010",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090208 - Disclosure - Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails",
     "shortName": "Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20200101to20201231",
      "decimals": "INF",
      "lang": null,
      "name": "ions:NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U011",
      "xsiNil": "false"
     }
    },
    "R26": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:InventoryRawMaterials",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090210 - Disclosure - Significant Accounting Policies, Inventory Valuation (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails",
     "shortName": "Significant Accounting Policies, Inventory Valuation (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:InventoryRawMaterials",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R27": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "ions:LesseeOperatingLeaseFreeRentPeriod",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090212 - Disclosure - Significant Accounting Policies, Leases (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails",
     "shortName": "Significant Accounting Policies, Leases (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331_PropertyPlantAndEquipmentByTypeAxis_BuildingMember",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "ions:LesseeOperatingLeaseFreeRentPeriod",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R28": {
     "firstAnchor": {
      "ancestors": [
       "us-gaap:EarningsPerShareDiluted",
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "2",
      "first": true,
      "lang": null,
      "name": "us-gaap:EarningsPerShareBasic",
      "reportCount": 1,
      "unitRef": "U004",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090214 - Disclosure - Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails",
     "shortName": "Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details)",
     "subGroupType": "details",
     "uniqueAnchor": null
    },
    "R29": {
     "firstAnchor": {
      "ancestors": [
       "span",
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember",
      "decimals": "2",
      "first": true,
      "lang": null,
      "name": "us-gaap:DebtInstrumentInterestRateStatedPercentage",
      "reportCount": 1,
      "unitRef": "U003",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090216 - Disclosure - Significant Accounting Policies, Convertible Debt (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails",
     "shortName": "Significant Accounting Policies, Convertible Debt (Details)",
     "subGroupType": "details",
     "uniqueAnchor": null
    },
    "R3": {
     "firstAnchor": {
      "ancestors": [
       "us-gaap:CommonStockParOrStatedValuePerShare",
       "span",
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "3",
      "first": true,
      "lang": null,
      "name": "us-gaap:CommonStockParOrStatedValuePerShare",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U004",
      "xsiNil": "false"
     },
     "groupType": "statement",
     "isDefault": "false",
     "longName": "010100 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical)",
     "role": "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical",
     "shortName": "CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical)",
     "subGroupType": "parenthetical",
     "uniqueAnchor": {
      "ancestors": [
       "us-gaap:CommonStockParOrStatedValuePerShare",
       "span",
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "3",
      "first": true,
      "lang": null,
      "name": "us-gaap:CommonStockParOrStatedValuePerShare",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U004",
      "xsiNil": "false"
     }
    },
    "R30": {
     "firstAnchor": null,
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090218 - Disclosure - Significant Accounting Policies, Segment Information (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesSegmentInformationDetails",
     "shortName": "Significant Accounting Policies, Segment Information (Details)",
     "subGroupType": "details",
     "uniqueAnchor": null
    },
    "R31": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:AllocatedShareBasedCompensationExpense",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090220 - Disclosure - Significant Accounting Policies, Stock-Based Compensation Expense (Details)",
     "role": "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails",
     "shortName": "Significant Accounting Policies, Stock-Based Compensation Expense (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:AllocatedShareBasedCompensationExpense",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R32": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "2",
      "first": true,
      "lang": null,
      "name": "ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U003",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090300 - Disclosure - Investments, Contract Maturity of Available-for-Sale Securities (Details)",
     "role": "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails",
     "shortName": "Investments, Contract Maturity of Available-for-Sale Securities (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "2",
      "first": true,
      "lang": null,
      "name": "ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U003",
      "xsiNil": "false"
     }
    },
    "R33": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "INF",
      "first": true,
      "lang": null,
      "name": "ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment",
      "reportCount": 1,
      "unitRef": "U010",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090302 - Disclosure - Investments, Summary of Investments (Details)",
     "role": "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails",
     "shortName": "Investments, Summary of Investments (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "-3",
      "lang": null,
      "name": "ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R34": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "0",
      "first": true,
      "lang": null,
      "name": "us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U011",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090304 - Disclosure - Investments, Investments Temporarily Impaired (Details)",
     "role": "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
     "shortName": "Investments, Investments Temporarily Impaired (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "ix:continuation",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331",
      "decimals": "0",
      "first": true,
      "lang": null,
      "name": "us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U011",
      "xsiNil": "false"
     }
    },
    "R35": {
     "firstAnchor": {
      "ancestors": [
       "us-gaap:DebtInstrumentInterestRateStatedPercentage",
       "span",
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember",
      "decimals": "5",
      "first": true,
      "lang": null,
      "name": "us-gaap:DebtInstrumentInterestRateStatedPercentage",
      "reportCount": 1,
      "unitRef": "U003",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090400 - Disclosure - Fair Value Measurements (Details)",
     "role": "http://ionispharma.com/role/FairValueMeasurementsDetails",
     "shortName": "Fair Value Measurements (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member",
      "decimals": "-5",
      "lang": null,
      "name": "us-gaap:NotesPayableFairValueDisclosure",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R36": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "ions:AmortizationPeriodForResearchAndDevelopmentExpenditures",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090500 - Disclosure - Income Taxes (Details)",
     "role": "http://ionispharma.com/role/IncomeTaxesDetails",
     "shortName": "Income Taxes (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "ions:AmortizationPeriodForResearchAndDevelopmentExpenditures",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R37": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090600 - Disclosure - Collaborative Arrangements and Licensing Agreements (Details)",
     "role": "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
     "shortName": "Collaborative Arrangements and Licensing Agreements (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220331_TypeOfArrangementAxis_BiogenCollaborationsMember",
      "decimals": "-8",
      "lang": null,
      "name": "ions:CumulativePaymentsReceived",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R38": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20210401to20210430",
      "decimals": "-5",
      "first": true,
      "lang": null,
      "name": "ions:CallSpread",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "090700 - Disclosure - Convertible Debt (Details)",
     "role": "http://ionispharma.com/role/ConvertibleDebtDetails",
     "shortName": "Convertible Debt (Details)",
     "subGroupType": "details",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "ix:continuation",
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20210401to20210430",
      "decimals": "-5",
      "first": true,
      "lang": null,
      "name": "ions:CallSpread",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R4": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "statement",
     "isDefault": "false",
     "longName": "020000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS",
     "role": "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
     "shortName": "CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "lang": null,
      "name": "us-gaap:CostOfGoodsAndServicesSold",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R5": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:NetIncomeLoss",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "statement",
     "isDefault": "false",
     "longName": "030000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS",
     "role": "http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss",
     "shortName": "CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "lang": null,
      "name": "us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R6": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20201231_StatementEquityComponentsAxis_CommonStockMember",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "statement",
     "isDefault": "false",
     "longName": "040000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY",
     "role": "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity",
     "shortName": "CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20201231_StatementEquityComponentsAxis_CommonStockMember",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R7": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "first": true,
      "lang": null,
      "name": "us-gaap:NetIncomeLoss",
      "reportCount": 1,
      "unitRef": "U002",
      "xsiNil": "false"
     },
     "groupType": "statement",
     "isDefault": "false",
     "longName": "050000 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS",
     "role": "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows",
     "shortName": "CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "td",
       "tr",
       "table",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": "-3",
      "lang": null,
      "name": "us-gaap:Depreciation",
      "reportCount": 1,
      "unique": true,
      "unitRef": "U002",
      "xsiNil": "false"
     }
    },
    "R8": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060100 - Disclosure - Basis of Presentation",
     "role": "http://ionispharma.com/role/BasisOfPresentation",
     "shortName": "Basis of Presentation",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    },
    "R9": {
     "firstAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:SignificantAccountingPoliciesTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     },
     "groupType": "disclosure",
     "isDefault": "false",
     "longName": "060200 - Disclosure - Significant Accounting Policies",
     "role": "http://ionispharma.com/role/SignificantAccountingPolicies",
     "shortName": "Significant Accounting Policies",
     "subGroupType": "",
     "uniqueAnchor": {
      "ancestors": [
       "div",
       "body",
       "html"
      ],
      "baseRef": "form10q.htm",
      "contextRef": "c20220101to20220331",
      "decimals": null,
      "first": true,
      "lang": "en-US",
      "name": "us-gaap:SignificantAccountingPoliciesTextBlock",
      "reportCount": 1,
      "unique": true,
      "unitRef": null,
      "xsiNil": "false"
     }
    }
   },
   "segmentCount": 69,
   "tag": {
    "dei_AmendmentFlag": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Boolean flag that is true when the XBRL content amends previously-filed or accepted submission.",
        "label": "Amendment Flag"
       }
      }
     },
     "localname": "AmendmentFlag",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "booleanItemType"
    },
    "dei_CityAreaCode": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Area code of city",
        "label": "City Area Code"
       }
      }
     },
     "localname": "CityAreaCode",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "normalizedStringItemType"
    },
    "dei_CoverAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Cover page.",
        "label": "Cover [Abstract]"
       }
      }
     },
     "localname": "CoverAbstract",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "xbrltype": "stringItemType"
    },
    "dei_CurrentFiscalYearEndDate": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "End date of current fiscal year in the format --MM-DD.",
        "label": "Current Fiscal Year End Date"
       }
      }
     },
     "localname": "CurrentFiscalYearEndDate",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "gMonthDayItemType"
    },
    "dei_DocumentFiscalPeriodFocus": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Document Fiscal Period Focus"
       }
      }
     },
     "localname": "DocumentFiscalPeriodFocus",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "fiscalPeriodItemType"
    },
    "dei_DocumentFiscalYearFocus": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "This is focus fiscal year of the document report in YYYY format. For a 2006 annual report, which may also provide financial information from prior periods, fiscal 2006 should be given as the fiscal year focus. Example: 2006.",
        "label": "Document Fiscal Year Focus"
       }
      }
     },
     "localname": "DocumentFiscalYearFocus",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "gYearItemType"
    },
    "dei_DocumentPeriodEndDate": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "For the EDGAR submission types of Form 8-K: the date of the report, the date of the earliest event reported; for the EDGAR submission types of Form N-1A: the filing date; for all other submission types: the end of the reporting or transition period.  The format of the date is YYYY-MM-DD.",
        "label": "Document Period End Date"
       }
      }
     },
     "localname": "DocumentPeriodEndDate",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "dateItemType"
    },
    "dei_DocumentQuarterlyReport": {
     "auth_ref": [
      "r542"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Boolean flag that is true only for a form used as an quarterly report.",
        "label": "Document Quarterly Report"
       }
      }
     },
     "localname": "DocumentQuarterlyReport",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "booleanItemType"
    },
    "dei_DocumentTransitionReport": {
     "auth_ref": [
      "r543"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Boolean flag that is true only for a form used as a transition report.",
        "label": "Document Transition Report"
       }
      }
     },
     "localname": "DocumentTransitionReport",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "booleanItemType"
    },
    "dei_DocumentType": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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'.",
        "label": "Document Type"
       }
      }
     },
     "localname": "DocumentType",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "submissionTypeItemType"
    },
    "dei_EntityAddressAddressLine1": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Address Line 1 such as Attn, Building Name, Street Name",
        "label": "Entity Address, Address Line One"
       }
      }
     },
     "localname": "EntityAddressAddressLine1",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "normalizedStringItemType"
    },
    "dei_EntityAddressCityOrTown": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Name of the City or Town",
        "label": "Entity Address, City or Town"
       }
      }
     },
     "localname": "EntityAddressCityOrTown",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "normalizedStringItemType"
    },
    "dei_EntityAddressPostalZipCode": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Code for the postal or zip code",
        "label": "Entity Address, Postal Zip Code"
       }
      }
     },
     "localname": "EntityAddressPostalZipCode",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "normalizedStringItemType"
    },
    "dei_EntityAddressStateOrProvince": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Name of the state or province.",
        "label": "Entity Address, State or Province"
       }
      }
     },
     "localname": "EntityAddressStateOrProvince",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "stateOrProvinceItemType"
    },
    "dei_EntityCentralIndexKey": {
     "auth_ref": [
      "r540"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "A unique 10-digit SEC-issued value to identify entities that have filed disclosures with the SEC. It is commonly abbreviated as CIK.",
        "label": "Entity Central Index Key"
       }
      }
     },
     "localname": "EntityCentralIndexKey",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "centralIndexKeyItemType"
    },
    "dei_EntityCommonStockSharesOutstanding": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Entity Common Stock, Shares Outstanding"
       }
      }
     },
     "localname": "EntityCommonStockSharesOutstanding",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "sharesItemType"
    },
    "dei_EntityCurrentReportingStatus": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Entity Current Reporting Status"
       }
      }
     },
     "localname": "EntityCurrentReportingStatus",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "yesNoItemType"
    },
    "dei_EntityEmergingGrowthCompany": {
     "auth_ref": [
      "r540"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Indicate if registrant meets the emerging growth company criteria.",
        "label": "Entity Emerging Growth Company"
       }
      }
     },
     "localname": "EntityEmergingGrowthCompany",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "booleanItemType"
    },
    "dei_EntityFileNumber": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Entity File Number"
       }
      }
     },
     "localname": "EntityFileNumber",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "fileNumberItemType"
    },
    "dei_EntityFilerCategory": {
     "auth_ref": [
      "r540"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Entity Filer Category"
       }
      }
     },
     "localname": "EntityFilerCategory",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "filerCategoryItemType"
    },
    "dei_EntityIncorporationStateCountryCode": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Two-character EDGAR code representing the state or country of incorporation.",
        "label": "Entity Incorporation, State or Country Code"
       }
      }
     },
     "localname": "EntityIncorporationStateCountryCode",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "edgarStateCountryItemType"
    },
    "dei_EntityInteractiveDataCurrent": {
     "auth_ref": [
      "r551"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Entity Interactive Data Current"
       }
      }
     },
     "localname": "EntityInteractiveDataCurrent",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "yesNoItemType"
    },
    "dei_EntityRegistrantName": {
     "auth_ref": [
      "r540"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The exact name of the entity filing the report as specified in its charter, which is required by forms filed with the SEC.",
        "label": "Entity Registrant Name"
       }
      }
     },
     "localname": "EntityRegistrantName",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "normalizedStringItemType"
    },
    "dei_EntityShellCompany": {
     "auth_ref": [
      "r540"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Boolean flag that is true when the registrant is a shell company as defined in Rule 12b-2 of the Exchange Act.",
        "label": "Entity Shell Company"
       }
      }
     },
     "localname": "EntityShellCompany",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "booleanItemType"
    },
    "dei_EntitySmallBusiness": {
     "auth_ref": [
      "r540"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Indicates that the company is a Smaller Reporting Company (SRC).",
        "label": "Entity Small Business"
       }
      }
     },
     "localname": "EntitySmallBusiness",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "booleanItemType"
    },
    "dei_EntityTaxIdentificationNumber": {
     "auth_ref": [
      "r540"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The Tax Identification Number (TIN), also known as an Employer Identification Number (EIN), is a unique 9-digit value assigned by the IRS.",
        "label": "Entity Tax Identification Number"
       }
      }
     },
     "localname": "EntityTaxIdentificationNumber",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "employerIdItemType"
    },
    "dei_LocalPhoneNumber": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Local phone number for entity.",
        "label": "Local Phone Number"
       }
      }
     },
     "localname": "LocalPhoneNumber",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "normalizedStringItemType"
    },
    "dei_Security12bTitle": {
     "auth_ref": [
      "r539"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Title of a 12(b) registered security.",
        "label": "Title of 12(b) Security"
       }
      }
     },
     "localname": "Security12bTitle",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "securityTitleItemType"
    },
    "dei_SecurityExchangeName": {
     "auth_ref": [
      "r541"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Name of the Exchange on which a security is registered.",
        "label": "Security Exchange Name"
       }
      }
     },
     "localname": "SecurityExchangeName",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "edgarExchangeCodeItemType"
    },
    "dei_TradingSymbol": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Trading symbol of an instrument as listed on an exchange.",
        "label": "Trading Symbol"
       }
      }
     },
     "localname": "TradingSymbol",
     "nsuri": "http://xbrl.sec.gov/dei/2021q4",
     "presentation": [
      "http://ionispharma.com/role/DocumentAndEntityInformation"
     ],
     "xbrltype": "tradingSymbolItemType"
    },
    "ions_AlnylamCollaborationMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Collaboration agreement entered into with Alnylam Pharmaceuticals, Inc. in March 2004 to develop and commercialize RNAi therapeutics.",
        "label": "Alnylam Collaboration [Member]",
        "terseLabel": "Alnylam [Member]"
       }
      }
     },
     "localname": "AlnylamCollaborationMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_AmortizationPeriodForResearchAndDevelopmentExpenditures": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amortization period for research and development expenditures under Internal Revenue Code Section 174, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.",
        "label": "Amortization Period for Research and Development Expenditures",
        "terseLabel": "Amortization period for research and development expenditures under IRC Section 174"
       }
      }
     },
     "localname": "AmortizationPeriodForResearchAndDevelopmentExpenditures",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/IncomeTaxesDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "ions_AstrazenecaCollaborationEplontersenMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Collaboration agreement entered into with AstraZeneca PLC in December 2021 to develop and commercialize eplontersen. Eplontersen, formerly known as IONIS-TTR-L and AKCEA-TTR-L, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive and fatal disease.",
        "label": "AstraZeneca Collaboration, Eplontersen [Member]",
        "terseLabel": "Eplontersen Collaboration with AstraZeneca [Member]"
       }
      }
     },
     "localname": "AstrazenecaCollaborationEplontersenMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails": {
       "order": 2.0,
       "parentTag": "ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage",
       "weight": 1.0
      }
     },
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.",
        "label": "Available-for-sale Securities, Debt Maturities, after One Through Two Years, Percentage",
        "terseLabel": "After one year but within two years"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails": {
       "order": 3.0,
       "parentTag": "ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage",
       "weight": 1.0
      }
     },
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Available-for-sale Securities, Debt Maturities, after Two Through Three and One Half Years, Percentage",
        "terseLabel": "After two years but within three and a half years"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The aggregate percentage of all available-for-sale debt securities, regardless of maturity.",
        "label": "Available-for-sale Securities, Debt Maturities, Total, Percentage",
        "totalLabel": "Total"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails": {
       "order": 1.0,
       "parentTag": "ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage",
       "weight": 1.0
      }
     },
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The percentage of available-for-sale debt securities that mature within one year of the balance sheet date.",
        "label": "Available-for-sale Securities, Debt Maturities, within One Year, Percentage",
        "terseLabel": "One year or less"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.",
        "label": "Available-for-sale Securities, Debt Maturities, within Two Years, Percentage",
        "terseLabel": "Percentage of available-for-sale securities with a maturity of less than two years"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_BicycleTherapeuticsPlcMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Bicycle Therapeutics plc is a clinical-stage biopharmaceutical company that is pioneering a unique class of chemically synthesized medicines based on its proprietary bicyclic peptide product platform to address therapeutic needs unreachable with existing treatment modalities.",
        "label": "Bicycle Therapeutics plc [Member]",
        "terseLabel": "Bicycle [Member]",
        "verboseLabel": "Bicycle Therapeutics plc [Member]"
       }
      }
     },
     "localname": "BicycleTherapeuticsPlcMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_BiogenCollaboration2013StrategicNeurologyMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Collaborative agreement entered into with Biogen Inc. in September 2013 focused on applying antisense technology to advance the treatment of neurodegenerative diseases.",
        "label": "Biogen Collaboration, 2013 Strategic Neurology [Member]",
        "terseLabel": "2013 Strategic Neurology [Member]",
        "verboseLabel": "Biogen 2013 Strategic Neurology [Member]"
       }
      }
     },
     "localname": "BiogenCollaboration2013StrategicNeurologyMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_BiogenCollaboration2018StrategicNeurologyMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Collaboration agreement entered into with Biogen Inc. in April 2018 to develop novel antisense drug candidates for a broad range of neurological diseases.",
        "label": "Biogen Collaboration, 2018 Strategic Neurology [Member]",
        "verboseLabel": "Biogen 2018 Strategic Neurology [Member]"
       }
      }
     },
     "localname": "BiogenCollaboration2018StrategicNeurologyMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Collaboration agreement entered into with Biogen Inc. in December 2017 to identify new antisense oligonucleotide drug candidates for the treatment of spinal muscular atrophy, or SMA.",
        "label": "Biogen Collaboration, New Antisense Medicines for Treatment of SMA [Member]",
        "terseLabel": "New Antisense Medicines for the Treatment of SMA [Member]"
       }
      }
     },
     "localname": "BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_BiogenCollaborationsMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Collaboration agreements entered into with Biogen Inc.",
        "label": "Biogen Collaborations [Member]",
        "terseLabel": "Biogen [Member]"
       }
      }
     },
     "localname": "BiogenCollaborationsMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_BiogenIncMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Biogen Inc. is an American multinational biotechnology company.",
        "label": "Biogen Inc. [Member]",
        "terseLabel": "Biogen [Member]"
       }
      }
     },
     "localname": "BiogenIncMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CallSpread": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Call Spread",
        "terseLabel": "Cost of call spread"
       }
      }
     },
     "localname": "CallSpread",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_ClinicalRawMaterialsMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Raw materials purchased for use in producing medicines that have alternative future uses until they are used.",
        "label": "Clinical Raw Materials [Member]",
        "terseLabel": "Clinical [Member]"
       }
      }
     },
     "localname": "ClinicalRawMaterialsMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeAgreementRevenueMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Revenue from research and development services performed under a collaborative agreement.",
        "label": "Collaborative Agreement Revenue [Member]",
        "terseLabel": "Collaborative Agreement Revenue [Member]"
       }
      }
     },
     "localname": "CollaborativeAgreementRevenueMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CollaborativeArrangementAndLicensingAgreementAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Collaborative Arrangement and Licensing Agreement [Abstract]"
       }
      }
     },
     "localname": "CollaborativeArrangementAndLicensingAgreementAbstract",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_CollaborativeArrangementsAndLicensingAgreementsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Collaborative Arrangements and Licensing Agreements [Abstract]"
       }
      }
     },
     "localname": "CollaborativeArrangementsAndLicensingAgreementsAbstract",
     "nsuri": "http://ionispharma.com/20220331",
     "xbrltype": "stringItemType"
    },
    "ions_CommercialMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Commercial [Member]",
        "terseLabel": "Commercial Revenue [Member]"
       }
      }
     },
     "localname": "CommercialMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CommercialRawMaterialsMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Raw materials purchased for manufacturing medicines for commercial production.",
        "label": "Commercial Raw Materials [Member]",
        "terseLabel": "Commercial [Member]"
       }
      }
     },
     "localname": "CommercialRawMaterialsMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ConvertibleNotesDisclosureLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Convertible Notes Disclosure [Line Items]",
        "terseLabel": "Convertible Notes [Abstract]"
       }
      }
     },
     "localname": "ConvertibleNotesDisclosureLineItems",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtTables"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_ConvertibleNotesDisclosureTable": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of information about income taxes.",
        "label": "Convertible Notes Disclosure [Table]"
       }
      }
     },
     "localname": "ConvertibleNotesDisclosureTable",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtTables"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_ConvertibleSeniorNotes0125PercentMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "0.125 percent convertible senior notes due December 2024.",
        "label": "Convertible Senior Notes 0.125 Percent [Member]",
        "terseLabel": "0.125 Percent Convertible Senior Notes [Member]",
        "verboseLabel": "0.125% Notes [Member]"
       }
      }
     },
     "localname": "ConvertibleSeniorNotes0125PercentMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical",
      "http://ionispharma.com/role/ConvertibleDebtDetails",
      "http://ionispharma.com/role/ConvertibleDebtTables",
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ConvertibleSeniorNotes0PercentMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "0 percent convertible senior notes due April 2026.",
        "label": "Convertible Senior Notes 0 Percent [Member]",
        "terseLabel": "0 Percent Convertible Senior Notes [Member]",
        "verboseLabel": "0% Notes [Member]"
       }
      }
     },
     "localname": "ConvertibleSeniorNotes0PercentMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical",
      "http://ionispharma.com/role/ConvertibleDebtDetails",
      "http://ionispharma.com/role/ConvertibleDebtTables",
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ConvertibleSeniorNotes1PercentMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "1 percent convertible senior notes due November 2021.",
        "label": "Convertible Senior Notes 1 Percent [Member]",
        "terseLabel": "1 Percent Convertible Senior Notes [Member]",
        "verboseLabel": "1% Notes [Member]"
       }
      }
     },
     "localname": "ConvertibleSeniorNotes1PercentMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_CumulativePaymentsReceived": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.",
        "label": "Cumulative payments received",
        "terseLabel": "Cumulative payments received"
       }
      }
     },
     "localname": "CumulativePaymentsReceived",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Debt Instrument, Convertible, Conversion Price including call spread",
        "terseLabel": "Effective conversion price per share with call spread (in dollars per share)"
       }
      }
     },
     "localname": "DebtInstrumentConvertibleConversionPriceIncludingCallSpread",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "perShareItemType"
    },
    "ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Debt Instrument, Convertible, Percentage of principal amount used as purchase price upon occurrence of fundamental change",
        "terseLabel": "Percentage of principal amount used as purchase price upon occurrence of fundamental change"
       }
      }
     },
     "localname": "DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_DebtInstrumentConvertibleSharesSubjectToConversion": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The number of shares of common stock subject to conversion if the debt was converted to equity.",
        "label": "Debt Instrument, Convertible, Shares Subject to Conversion",
        "terseLabel": "Total shares of common stock subject to conversion (in shares)"
       }
      }
     },
     "localname": "DebtInstrumentConvertibleSharesSubjectToConversion",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "sharesItemType"
    },
    "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails": {
       "order": 2.0,
       "parentTag": "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Debt Securities, Available-for-sale and Equity Securities, FV-NI",
        "terseLabel": "Estimated fair value"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Debt Securities, Available-for-sale and Equity Securities, FV-NI, Cost",
        "totalLabel": "Amortized cost"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails": {
       "order": 0.0,
       "parentTag": "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Gain",
        "terseLabel": "Gross unrealized gains"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails": {
       "order": 1.0,
       "parentTag": "ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Debt Securities, Available-for-sale and Equity Securities, FV-NI, Gross Unrealized Loss",
        "negatedLabel": "Gross unrealized losses"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_EplontersenJointDevelopmentRevenueMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Joint development revenue for eplontersen.",
        "label": "Eplontersen Joint Development Revenue [Member]",
        "terseLabel": "Eplontersen Joint Development Revenue [Member]"
       }
      }
     },
     "localname": "EplontersenJointDevelopmentRevenueMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_EquitySecuritiesPrivateCompaniesMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Ownership interest or right to acquire or dispose of ownership interest in private corporations and other legal entities for which ownership interest is represented by shares of common or preferred stock, convertible securities, stock rights, or stock warrants.",
        "label": "Equity Securities, Private Companies [Member]",
        "terseLabel": "Equity Securities in Private Companies [Member]"
       }
      }
     },
     "localname": "EquitySecuritiesPrivateCompaniesMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_EquitySecuritiesPubliclyTradedCompaniesMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Ownership interest or right to acquire or dispose of ownership interest in publicly traded corporations and other legal entities for which ownership interest is represented by shares of common or preferred stock, convertible securities, stock rights, or stock warrants.",
        "label": "Equity Securities, Publicly Traded Companies [Member]",
        "terseLabel": "Equity Securities in Publicly Traded Company [Member]"
       }
      }
     },
     "localname": "EquitySecuritiesPubliclyTradedCompaniesMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Dynacure is a biotechnology company developing new treatments for patients affected by serious orphan disorders. Suzhou-Ribo Life Science Co., Ltd. (Suzhou-Ribo) is a small interfering RNA (siRNA) drug development company in China, devoted to the development of innovative nucleic acid therapeutic drugs and related products. 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.",
        "label": "Investments in Dynacure SAS, Suzhou-Ribo Life Science Co., Ltd. and Aro Biotherapeutics [Member]",
        "terseLabel": "Investments in Dynacure, Suzhou-Ribo and Aro Biotherapeutics [Member]"
       }
      }
     },
     "localname": "InvestmentsInDynacureSasSuzhouRiboLifeScienceCoLtdAndAroBiotherapeuticsMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_Ion306Member": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "ION306 is an antisense oligonucleotide or ASO that is designed to boost production of the survival motor neuron protein, known as SMN.",
        "label": "Ion306 [Member]",
        "terseLabel": "ION306 [Member]"
       }
      }
     },
     "localname": "Ion306Member",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_Ion541Member": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "ION541, also known as BIIB105, is an investigational antisense medicine targeting ataxin 2 (ATXN2) RNA.",
        "label": "Ion541 [Member]",
        "terseLabel": "ION541 [Member]"
       }
      }
     },
     "localname": "Ion541Member",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_Ion859Member": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "ION859 (BIIB094) is an antisense medicine designed to inhibit the production of the Leucine Rich Repeat Kinase 2, or LRRK2, protein as a potential therapy for Parkinson's disease, or PD.",
        "label": "Ion859 [Member]",
        "terseLabel": "ION859 [Member]"
       }
      }
     },
     "localname": "Ion859Member",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_LesseeOperatingLeaseFreeRentPeriod": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Period of time lessee will receive free rent under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.",
        "label": "Lessee, Operating Lease, Free Rent Period",
        "terseLabel": "Free rent period"
       }
      }
     },
     "localname": "LesseeOperatingLeaseFreeRentPeriod",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "ions_LicensingAndOtherRoyaltiesMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Revenue from license fees and other royalties, excluding royalties from the sale of SPINRAZA.",
        "label": "Licensing and Other Royalties [Member]",
        "verboseLabel": "Licensing and Other Royalty Revenue [Member]"
       }
      }
     },
     "localname": "LicensingAndOtherRoyaltiesMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_LongTermObligationsExcludingConvertibleDebtCurrent": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 6.0,
       "parentTag": "us-gaap_LiabilitiesCurrent",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of long-term debt and lease obligations, excluding convertible debt, classified as current.",
        "label": "Long-term Obligations, Excluding Convertible Debt, Current",
        "terseLabel": "Current portion of long-term obligations"
       }
      }
     },
     "localname": "LongTermObligationsExcludingConvertibleDebtCurrent",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_LongTermObligationsExcludingConvertibleDebtNoncurrent": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 4.0,
       "parentTag": "us-gaap_Liabilities",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of long-term debt and lease obligations, excluding convertible debt, classified as noncurrent.",
        "label": "Long-term Obligations Excluding Convertible Debt, Noncurrent",
        "terseLabel": "Long-term obligations, less current portion"
       }
      }
     },
     "localname": "LongTermObligationsExcludingConvertibleDebtNoncurrent",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_MaximumContractMaturityPeriodRange1": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Maximum contract maturity period, range 1",
        "terseLabel": "Maximum contract maturity period, range 1"
       }
      }
     },
     "localname": "MaximumContractMaturityPeriodRange1",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "ions_MaximumContractMaturityPeriodRange2": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Maximum contract maturity period, range 2",
        "terseLabel": "Maximum contract maturity period, range 2"
       }
      }
     },
     "localname": "MaximumContractMaturityPeriodRange2",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "ions_MaximumContractMaturityPeriodRange3": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Maximum contract maturity period, range 3",
        "terseLabel": "Maximum contract maturity period, range 3"
       }
      }
     },
     "localname": "MaximumContractMaturityPeriodRange3",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "ions_NextPotentialPayment": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The next potential payment to be earned under the collaboration agreement.",
        "label": "Next potential payment",
        "terseLabel": "Next prospective payment"
       }
      }
     },
     "localname": "NextPotentialPayment",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_NonCashCapitalAndPatentExpenditures": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Future cash outflow to pay for purchases of fixed assets and patents that have been incurred.",
        "label": "Non-cash Capital and Patent Expenditures",
        "terseLabel": "Amounts accrued for capital and patent expenditures"
       }
      }
     },
     "localname": "NonCashCapitalAndPatentExpenditures",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_NumberOfAgreementsWithCollaborationPartner": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The number of agreements entered into with the collaboration partner.",
        "label": "Number of agreements with collaboration partner",
        "terseLabel": "Number of agreements"
       }
      }
     },
     "localname": "NumberOfAgreementsWithCollaborationPartner",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Number of investments in privately-held companies that were revalued since the companies sold additional equity securities.",
        "label": "Number of investments in privately-held companies that were revalued",
        "terseLabel": "Number of investments in privately held companies that were revalued"
       }
      }
     },
     "localname": "NumberOfInvestmentsInPrivatelyHeldCompaniesThatWereRevalued",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfMaterialComponents": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.",
        "label": "Number of material components",
        "terseLabel": "Number of material components"
       }
      }
     },
     "localname": "NumberOfMaterialComponents",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Number of Privately-Held Companies in which Entity has Equity Investment",
        "terseLabel": "Number of privately held companies in which there is an equity ownership interest of less than 20%",
        "verboseLabel": "Number of private companies in which there is an equity ownership interest of less than 20%"
       }
      }
     },
     "localname": "NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Number of Publicly-Held Companies in which Entity has Equity Investment",
        "terseLabel": "Number of publicly held companies in which there is an equity ownership interest of less than 20%",
        "verboseLabel": "Number of public companies in which there is an equity ownership interest of less than 20%"
       }
      }
     },
     "localname": "NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Number of publicly-traded companies in which the entity has an equity investment included in other current assets.",
        "label": "Number of Publicly-Traded Companies in which Entity has Equity Investment included in Other Current Assets",
        "terseLabel": "Number of publicly traded companies in which there is an investment included in other current assets"
       }
      }
     },
     "localname": "NumberOfPubliclyTradedCompaniesInWhichEntityHasEquityInvestmentIncludedInOtherCurrentAssets",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfSignificantCustomers": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The number of significant customers with which the Company does business.",
        "label": "Number of Significant Customers",
        "terseLabel": "Number of significant customers"
       }
      }
     },
     "localname": "NumberOfSignificantCustomers",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_NumberOfTargetsAdvanced": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Number of targets advanced under the collaboration agreement.",
        "label": "Number of targets advanced",
        "terseLabel": "Number of targets advanced"
       }
      }
     },
     "localname": "NumberOfTargetsAdvanced",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.",
        "label": "Percentage of costs associated with ongoing global Phase 3 development program paid by Collaboration Partner",
        "terseLabel": "Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca"
       }
      }
     },
     "localname": "PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_PeriodAfterBillingWhenPaymentIsReceived": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Period after billing when payment is received",
        "terseLabel": "Period of time after billing when payment is received"
       }
      }
     },
     "localname": "PeriodAfterBillingWhenPaymentIsReceived",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "ions_ProqrTherapeuticsNVMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "ProQR Therapeutics N.V. is a clinical stage biotech company that discovers and develops unique Ribonucleic acid (RNA) therapies for severe genetic disorders, specialized in retinal diseases.",
        "label": "ProQR Therapeutics N.V. [Member]",
        "terseLabel": "ProQR [Member]",
        "verboseLabel": "ProQR Therapeutics N.V. [Member]"
       }
      }
     },
     "localname": "ProqrTherapeuticsNVMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ResearchAndDevelopmentRevenueMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Revenue from research and development services.",
        "label": "Research and Development Revenue [Member]",
        "terseLabel": "R&amp;D Revenue [Member]",
        "verboseLabel": "Research and Development Revenue [Member]"
       }
      }
     },
     "localname": "ResearchAndDevelopmentRevenueMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ResearchDevelopmentAndPatentExpense": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 2.0,
       "parentTag": "us-gaap_CostsAndExpenses",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Research, Development and Patent Expense",
        "terseLabel": "Research, development and patent"
       }
      }
     },
     "localname": "ResearchDevelopmentAndPatentExpense",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_ResearchDevelopmentAndPatentExpensesMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Primary financial statement caption encompassing research, development and patent expenses.",
        "label": "Research, Development and Patent Expenses [Member]",
        "verboseLabel": "Research, Development and Patent Expense [Member]"
       }
      }
     },
     "localname": "ResearchDevelopmentAndPatentExpensesMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The number of separate performance obligations under the collaboration agreement.",
        "label": "Revenue from Contract with Customer, Number of separate performance obligations",
        "terseLabel": "Number of separate performance obligations"
       }
      }
     },
     "localname": "RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_RevenueFromContractWithCustomerTransactionPrice": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.",
        "label": "Revenue from Contract with Customer, Transaction Price",
        "terseLabel": "Transaction price"
       }
      }
     },
     "localname": "RevenueFromContractWithCustomerTransactionPrice",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_RevenueFromContractWithCustomerTransactionPriceAdditions": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The additional amount of consideration the Company earned under the collaboration agreement that is added to the transaction price.",
        "label": "Revenue from Contract with Customer, Transaction Price, Additions",
        "terseLabel": "Milestone payment received and added to transaction price"
       }
      }
     },
     "localname": "RevenueFromContractWithCustomerTransactionPriceAdditions",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in October 2018 to develop IONIS-FB-L for the treatment of complement-mediated diseases.",
        "label": "Roche Collaboration, Ionis-Fb-L for Complement-Mediated Diseases [Member]",
        "verboseLabel": "IONIS-FB-L for Complement-Mediated Diseases [Member]"
       }
      }
     },
     "localname": "RocheCollaborationIonisFbLForComplementMediatedDiseasesMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_SecuritiesWithMaturityOfMoreThanOneYearMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Represents investment securities with an expected maturity of more than one year.",
        "label": "Securities with Maturity of More than One Year [Member]"
       }
      }
     },
     "localname": "SecuritiesWithMaturityOfMoreThanOneYearMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_SecuritiesWithMaturityOfOneYearOrLessMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Represents investment securities with an expected maturity of one year or less.",
        "label": "Securities with Maturity of One Year or Less [Member]"
       }
      }
     },
     "localname": "SecuritiesWithMaturityOfOneYearOrLessMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Number of separate performance periods under share-based payment arrangement.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Number of Performance Periods",
        "terseLabel": "Number of performance periods"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Number of units guaranteed to vest under share-based payment arrangement.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Number of units guaranteed to vest",
        "terseLabel": "Number of units guaranteed to vest (in shares)"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "sharesItemType"
    },
    "ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Percentage of units guaranteed to vest under share-based payment arrangement.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Percentage of units guaranteed to vest",
        "terseLabel": "Percentage of units guaranteed to vest"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "ions_ShareBasedPaymentArrangementBoardOfDirectorMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Share-based Payment Arrangement, Board of Director [Member]",
        "terseLabel": "Board of Directors [Member]"
       }
      }
     },
     "localname": "ShareBasedPaymentArrangementBoardOfDirectorMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Share-based payment arrangement granting right, subject to vesting and other restrictions, to purchase or sell certain number of shares at predetermined price for specified period of time granted on January 1, 2022 and thereafter.",
        "label": "Share-based Payment Arrangement, Options Granted on January 1, 2022 and Thereafter [Member]",
        "verboseLabel": "Stock Options Granted on January 1, 2022 and Thereafter [Member]"
       }
      }
     },
     "localname": "ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Share-based payment arrangement granting right, subject to vesting and other restrictions, to purchase or sell certain number of shares at predetermined price for specified period of time granted prior to January 1, 2022.",
        "label": "Share-based Payment Arrangement, Options Granted Prior to January 1, 2022 [Member]",
        "terseLabel": "Stock Options Granted Prior to January 1, 2022 [Member]"
       }
      }
     },
     "localname": "ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_SignificantPartnersAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Significant Partners [Abstract]"
       }
      }
     },
     "localname": "SignificantPartnersAbstract",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "ions_SpinrazaRoyaltiesMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Royalty revenues from the sale of SPINRAZA (nusinersen).",
        "label": "Spinraza Royalties [Member]",
        "terseLabel": "SPINRAZA Royalties [Member]"
       }
      }
     },
     "localname": "SpinrazaRoyaltiesMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_TwoSignificantCustomersMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Two Significant Customers [Member]",
        "terseLabel": "Two Significant Customers [Member]"
       }
      }
     },
     "localname": "TwoSignificantCustomersMember",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "ions_UpfrontPaymentReceived": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The amount of upfront payments received during the period under the collaboration agreement.",
        "label": "Upfront payment received",
        "terseLabel": "Upfront payment received"
       }
      }
     },
     "localname": "UpfrontPaymentReceived",
     "nsuri": "http://ionispharma.com/20220331",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "srt_EquityMethodInvesteeNameDomain": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Investment, Name [Domain]"
       }
      }
     },
     "localname": "EquityMethodInvesteeNameDomain",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_ExecutiveOfficerMember": {
     "auth_ref": [
      "r173"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Executive Officer [Member]",
        "terseLabel": "Executive Officers [Member]"
       }
      }
     },
     "localname": "ExecutiveOfficerMember",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_MajorCustomersAxis": {
     "auth_ref": [
      "r172",
      "r307",
      "r312",
      "r515"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Customer [Axis]"
       }
      }
     },
     "localname": "MajorCustomersAxis",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "srt_MaximumMember": {
     "auth_ref": [
      "r252",
      "r287",
      "r328",
      "r329",
      "r448",
      "r449",
      "r450",
      "r451",
      "r452",
      "r453",
      "r472",
      "r513",
      "r516",
      "r537",
      "r538"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Maximum [Member]"
       }
      }
     },
     "localname": "MaximumMember",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_MinimumMember": {
     "auth_ref": [
      "r252",
      "r287",
      "r328",
      "r329",
      "r448",
      "r449",
      "r450",
      "r451",
      "r452",
      "r453",
      "r472",
      "r513",
      "r516",
      "r537",
      "r538"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Minimum [Member]"
       }
      }
     },
     "localname": "MinimumMember",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_NameOfMajorCustomerDomain": {
     "auth_ref": [
      "r172",
      "r307",
      "r312",
      "r515"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Customer [Domain]"
       }
      }
     },
     "localname": "NameOfMajorCustomerDomain",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_ProductOrServiceAxis": {
     "auth_ref": [
      "r170",
      "r307",
      "r310",
      "r478",
      "r512",
      "r514"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Products and Services [Axis]"
       }
      }
     },
     "localname": "ProductOrServiceAxis",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "srt_ProductsAndServicesDomain": {
     "auth_ref": [
      "r170",
      "r307",
      "r310",
      "r478",
      "r512",
      "r514"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Products and Services [Domain]"
       }
      }
     },
     "localname": "ProductsAndServicesDomain",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_RangeAxis": {
     "auth_ref": [
      "r252",
      "r287",
      "r319",
      "r328",
      "r329",
      "r448",
      "r449",
      "r450",
      "r451",
      "r452",
      "r453",
      "r472",
      "r513",
      "r516",
      "r537",
      "r538"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Statistical Measurement [Axis]"
       }
      }
     },
     "localname": "RangeAxis",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "srt_RangeMember": {
     "auth_ref": [
      "r252",
      "r287",
      "r319",
      "r328",
      "r329",
      "r448",
      "r449",
      "r450",
      "r451",
      "r452",
      "r453",
      "r472",
      "r513",
      "r516",
      "r537",
      "r538"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Statistical Measurement [Domain]"
       }
      }
     },
     "localname": "RangeMember",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis": {
     "auth_ref": [
      "r201"
     ],
     "lang": {
      "en-us": {
       "role": {
        "label": "Investment, Name [Axis]"
       }
      }
     },
     "localname": "ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis",
     "nsuri": "http://fasb.org/srt/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AccountingPoliciesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Significant Accounting Policies [Abstract]"
       }
      }
     },
     "localname": "AccountingPoliciesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_AccountsPayableCurrent": {
     "auth_ref": [
      "r30",
      "r441"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 0.0,
       "parentTag": "us-gaap_LiabilitiesCurrent",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Accounts Payable, Current",
        "terseLabel": "Accounts payable"
       }
      }
     },
     "localname": "AccountsPayableCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccountsReceivableMember": {
     "auth_ref": [
      "r536"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Due from customers or clients for goods or services that have been delivered or sold.",
        "label": "Accounts Receivable [Member]",
        "verboseLabel": "Contracts Receivables [Member]"
       }
      }
     },
     "localname": "AccountsReceivableMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments": {
     "auth_ref": [
      "r90"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 4.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Accretion (Amortization) of Discounts and Premiums, Investments",
        "negatedTerseLabel": "Amortization of premium on investments, net"
       }
      }
     },
     "localname": "AccretionAmortizationOfDiscountsAndPremiumsInvestments",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccruedIncomeTaxesCurrent": {
     "auth_ref": [
      "r14",
      "r483",
      "r499"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 4.0,
       "parentTag": "us-gaap_LiabilitiesCurrent",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Accrued Income Taxes, Current",
        "terseLabel": "Income taxes payable"
       }
      }
     },
     "localname": "AccruedIncomeTaxesCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccruedLiabilitiesCurrent": {
     "auth_ref": [
      "r33"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 2.0,
       "parentTag": "us-gaap_LiabilitiesCurrent",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Accrued Liabilities, Current",
        "terseLabel": "Accrued liabilities"
       }
      }
     },
     "localname": "AccruedLiabilitiesCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax": {
     "auth_ref": [
      "r20",
      "r49",
      "r50",
      "r51",
      "r501",
      "r521",
      "r522"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 3.0,
       "parentTag": "us-gaap_StockholdersEquity",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Accumulated Other Comprehensive Income (Loss), Net of Tax",
        "verboseLabel": "Accumulated other comprehensive loss"
       }
      }
     },
     "localname": "AccumulatedOtherComprehensiveIncomeLossNetOfTax",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AccumulatedOtherComprehensiveIncomeMember": {
     "auth_ref": [
      "r48",
      "r51",
      "r58",
      "r59",
      "r60",
      "r109",
      "r110",
      "r111",
      "r391",
      "r517",
      "r518",
      "r552"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Accumulated increase (decrease) in equity from transactions and other events and circumstances from non-owner sources, attributable to the parent. Excludes net income (loss), and accumulated changes in equity from transactions resulting from investments by owners and distributions to owners.",
        "label": "Accumulated Other Comprehensive Loss [Member]"
       }
      }
     },
     "localname": "AccumulatedOtherComprehensiveIncomeMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_AdditionalPaidInCapitalCommonStock": {
     "auth_ref": [
      "r18"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 2.0,
       "parentTag": "us-gaap_StockholdersEquity",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Additional Paid in Capital, Common Stock",
        "terseLabel": "Additional paid-in capital"
       }
      }
     },
     "localname": "AdditionalPaidInCapitalCommonStock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AdditionalPaidInCapitalMember": {
     "auth_ref": [
      "r109",
      "r110",
      "r111",
      "r352",
      "r353",
      "r354",
      "r404"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Excess of issue price over par or stated value of the entity's capital stock and amounts received from other transactions involving the entity's stock or stockholders.",
        "label": "Additional Paid In Capital [Member]"
       }
      }
     },
     "localname": "AdditionalPaidInCapitalMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of decrease to equity for grantee's tax withholding obligation for award under share-based payment arrangement.",
        "label": "Share-based Payment Arrangement, Decrease for Tax Withholding Obligation",
        "negatedLabel": "Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options"
       }
      }
     },
     "localname": "AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue": {
     "auth_ref": [
      "r331",
      "r334",
      "r358",
      "r359"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of increase to additional paid-in capital (APIC) for recognition of cost for award under share-based payment arrangement.",
        "label": "APIC, Share-based Payment Arrangement, Increase for Cost Recognition",
        "terseLabel": "Stock-based compensation expense"
       }
      }
     },
     "localname": "AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Adjustments to reconcile net loss to net cash used in operating activities:"
       }
      }
     },
     "localname": "AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AllocatedShareBasedCompensationExpense": {
     "auth_ref": [
      "r334",
      "r348",
      "r357"
     ],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of expense for award under share-based payment arrangement. Excludes amount capitalized.",
        "label": "Share-based Payment Arrangement, Expense",
        "verboseLabel": "Non-cash stock-based compensation expense"
       }
      }
     },
     "localname": "AllocatedShareBasedCompensationExpense",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AmortizationOfFinancingCosts": {
     "auth_ref": [
      "r66",
      "r89",
      "r272",
      "r433"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 5.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of amortization expense attributable to debt issuance costs.",
        "label": "Amortization of Debt Issuance Costs",
        "terseLabel": "Amortization of debt issuance costs"
       }
      }
     },
     "localname": "AmortizationOfFinancingCosts",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AmortizationOfIntangibleAssets": {
     "auth_ref": [
      "r89",
      "r225",
      "r228"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 3.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Amortization of Intangible Assets",
        "terseLabel": "Amortization of patents"
       }
      }
     },
     "localname": "AmortizationOfIntangibleAssets",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ArrangementsAndNonarrangementTransactionsMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Collaborative arrangement and arrangement other than collaborative applicable to revenue-generating activity or operations.",
        "label": "Arrangements and Non-arrangement Transactions [Domain]"
       }
      }
     },
     "localname": "ArrangementsAndNonarrangementTransactionsMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_Assets": {
     "auth_ref": [
      "r102",
      "r153",
      "r162",
      "r168",
      "r203",
      "r238",
      "r239",
      "r240",
      "r241",
      "r242",
      "r243",
      "r244",
      "r245",
      "r246",
      "r247",
      "r248",
      "r387",
      "r392",
      "r419",
      "r439",
      "r441",
      "r481",
      "r498"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Assets",
        "totalLabel": "Total assets"
       }
      }
     },
     "localname": "Assets",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AssetsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Assets [Abstract]",
        "terseLabel": "ASSETS"
       }
      }
     },
     "localname": "AssetsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AssetsCurrent": {
     "auth_ref": [
      "r6",
      "r7",
      "r45",
      "r102",
      "r203",
      "r238",
      "r239",
      "r240",
      "r241",
      "r242",
      "r243",
      "r244",
      "r245",
      "r246",
      "r247",
      "r248",
      "r387",
      "r392",
      "r419",
      "r439",
      "r441"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 1.0,
       "parentTag": "us-gaap_Assets",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Assets, Current",
        "totalLabel": "Total current assets"
       }
      }
     },
     "localname": "AssetsCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AssetsCurrentAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Assets, Current [Abstract]",
        "terseLabel": "Current assets:"
       }
      }
     },
     "localname": "AssetsCurrentAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AssetsFairValueDisclosure": {
     "auth_ref": [
      "r407"
     ],
     "calculation": {
      "http://ionispharma.com/role/FairValueMeasurementsDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Fair value portion of probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.",
        "label": "Assets, Fair Value Disclosure",
        "totalLabel": "Total"
       }
      }
     },
     "localname": "AssetsFairValueDisclosure",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax": {
     "auth_ref": [
      "r186"
     ],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails": {
       "order": 0.0,
       "parentTag": "us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Debt Securities, Available-for-sale, Accumulated Gross Unrealized Gain, before Tax",
        "terseLabel": "Gross unrealized gains"
       }
      }
     },
     "localname": "AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax": {
     "auth_ref": [
      "r187"
     ],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Debt Securities, Available-for-sale, Accumulated Gross Unrealized Loss, before Tax",
        "negatedLabel": "Gross unrealized losses"
       }
      }
     },
     "localname": "AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis": {
     "auth_ref": [
      "r184",
      "r212"
     ],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).",
        "label": "Debt Securities, Available-for-sale, Amortized Cost",
        "totalLabel": "Amortized cost"
       }
      }
     },
     "localname": "AvailableForSaleDebtSecuritiesAmortizedCostBasis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Debt Securities, Available-for-sale [Abstract]",
        "terseLabel": "Temporarily Impaired Investments [Abstract]"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Debt Securities, Available-for-sale, Unrealized Loss Position, Accumulated Loss [Abstract]",
        "terseLabel": "Unrealized Losses [Abstract]"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Available-for-sale Securities, Continuous Unrealized Loss Position, Qualitative Disclosure [Abstract]",
        "terseLabel": "Estimated Fair Value [Abstract]"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Available-for-sale Securities, Debt Maturities [Abstract]",
        "terseLabel": "Contract Maturity of Available-for-Sale Securities [Abstract]"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtMaturitiesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsContractMaturityOfAvailableforsaleSecuritiesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesDebtSecurities": {
     "auth_ref": [
      "r180",
      "r185",
      "r212",
      "r486"
     ],
     "calculation": {
      "http://ionispharma.com/role/FairValueMeasurementsDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_AssetsFairValueDisclosure",
       "weight": 1.0
      },
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails": {
       "order": 4.0,
       "parentTag": "us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).",
        "label": "Debt Securities, Available-for-sale",
        "terseLabel": "Estimated fair value",
        "verboseLabel": "Available-for-sale securities"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtSecurities",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent": {
     "auth_ref": [
      "r182",
      "r212"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 1.0,
       "parentTag": "us-gaap_AssetsCurrent",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Debt Securities, Available-for-sale, Current",
        "terseLabel": "Short-term investments"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesDebtSecuritiesCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Summary of Investments [Abstract]"
       }
      }
     },
     "localname": "AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_AwardTypeAxis": {
     "auth_ref": [
      "r335",
      "r350"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by type of award under share-based payment arrangement.",
        "label": "Award Type [Axis]"
       }
      }
     },
     "localname": "AwardTypeAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_BalanceSheetLocationAxis": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by location on balance sheet (statement of financial position).",
        "label": "Balance Sheet Location [Axis]"
       }
      }
     },
     "localname": "BalanceSheetLocationAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_BalanceSheetLocationDomain": {
     "auth_ref": [
      "r400",
      "r401"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Location in the balance sheet (statement of financial position).",
        "label": "Balance Sheet Location [Domain]"
       }
      }
     },
     "localname": "BalanceSheetLocationDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_BasisOfAccountingPolicyPolicyTextBlock": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Basis of Presentation"
       }
      }
     },
     "localname": "BasisOfAccountingPolicyPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/BasisOfPresentationPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_BuildingMember": {
     "auth_ref": [
      "r232"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Facility held for productive use including, but not limited to, office, production, storage and distribution facilities.",
        "label": "Building [Member]",
        "terseLabel": "Office Space in Boston, Massachusetts [Member]"
       }
      }
     },
     "localname": "BuildingMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CashAndCashEquivalentsAtCarryingValue": {
     "auth_ref": [
      "r4",
      "r27",
      "r91"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 0.0,
       "parentTag": "us-gaap_AssetsCurrent",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Cash and Cash Equivalents, at Carrying Value",
        "terseLabel": "Cash and cash equivalents"
       }
      }
     },
     "localname": "CashAndCashEquivalentsAtCarryingValue",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CashAndCashEquivalentsFairValueDisclosure": {
     "auth_ref": [],
     "calculation": {
      "http://ionispharma.com/role/FairValueMeasurementsDetails": {
       "order": 0.0,
       "parentTag": "us-gaap_AssetsFairValueDisclosure",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Cash and Cash Equivalents, Fair Value Disclosure",
        "terseLabel": "Cash equivalents"
       }
      }
     },
     "localname": "CashAndCashEquivalentsFairValueDisclosure",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CashAndCashEquivalentsMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Cash and Cash Equivalents [Member]"
       }
      }
     },
     "localname": "CashAndCashEquivalentsMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Cash, Cash Equivalents, and Short-term Investments [Abstract]",
        "terseLabel": "Cash, Cash Equivalents and Investments [Abstract]"
       }
      }
     },
     "localname": "CashCashEquivalentsAndShortTermInvestmentsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents": {
     "auth_ref": [
      "r83",
      "r91",
      "r93"
     ],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Cash, Cash Equivalents, Restricted Cash and Restricted Cash Equivalents",
        "periodEndLabel": "Cash and cash equivalents at end of period",
        "periodStartLabel": "Cash and cash equivalents at beginning of period"
       }
      }
     },
     "localname": "CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect": {
     "auth_ref": [
      "r83",
      "r422"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Cash, Cash Equivalents, Restricted Cash and Restricted Cash Equivalents, Period Increase (Decrease), Including Exchange Rate Effect",
        "totalLabel": "Net (decrease) increase in cash and cash equivalents"
       }
      }
     },
     "localname": "CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Cash Flow, Noncash Investing and Financing Activities Disclosure [Abstract]",
        "terseLabel": "Supplemental disclosures of non-cash investing and financing activities:"
       }
      }
     },
     "localname": "CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_CollaborativeArrangementDisclosureTextBlock": {
     "auth_ref": [
      "r379",
      "r380",
      "r382"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Collaborative Arrangement Disclosure [Text Block]",
        "terseLabel": "Collaborative Arrangements and Licensing Agreements"
       }
      }
     },
     "localname": "CollaborativeArrangementDisclosureTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreements"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]"
       }
      }
     },
     "localname": "CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_CommonStockMember": {
     "auth_ref": [
      "r109",
      "r110",
      "r404"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Stock that is subordinate to all other stock of the issuer.",
        "label": "Common Stock [Member]"
       }
      }
     },
     "localname": "CommonStockMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CommonStockParOrStatedValuePerShare": {
     "auth_ref": [
      "r17"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Face amount or stated value per share of common stock.",
        "label": "Common Stock, Par or Stated Value Per Share",
        "terseLabel": "Common stock, par value (in dollars per share)"
       }
      }
     },
     "localname": "CommonStockParOrStatedValuePerShare",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical"
     ],
     "xbrltype": "perShareItemType"
    },
    "us-gaap_CommonStockSharesAuthorized": {
     "auth_ref": [
      "r17"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The maximum number of common shares permitted to be issued by an entity's charter and bylaws.",
        "label": "Common Stock, Shares Authorized",
        "terseLabel": "Common stock, shares authorized (in shares)"
       }
      }
     },
     "localname": "CommonStockSharesAuthorized",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_CommonStockSharesIssued": {
     "auth_ref": [
      "r17"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Common Stock, Shares, Issued",
        "terseLabel": "Common stock, shares issued (in shares)"
       }
      }
     },
     "localname": "CommonStockSharesIssued",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_CommonStockSharesOutstanding": {
     "auth_ref": [
      "r17",
      "r289"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Number of shares of common stock outstanding. Common stock represent the ownership interest in a corporation.",
        "label": "Common Stock, Shares, Outstanding",
        "terseLabel": "Common stock, shares outstanding (in shares)"
       }
      }
     },
     "localname": "CommonStockSharesOutstanding",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_CommonStockValue": {
     "auth_ref": [
      "r17",
      "r441"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 1.0,
       "parentTag": "us-gaap_StockholdersEquity",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Common Stock, Value, Issued",
        "verboseLabel": "Common stock, $0.001 par value; 300,000,000 shares authorized, 141,753,122 and 141,210,015 shares issued and outstanding at March 31, 2022 (unaudited) and December 31, 2021, respectively"
       }
      }
     },
     "localname": "CommonStockValue",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ComprehensiveIncomeNetOfTax": {
     "auth_ref": [
      "r53",
      "r55",
      "r56",
      "r64",
      "r489",
      "r506"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Comprehensive Income (Loss), Net of Tax, Attributable to Parent",
        "totalLabel": "Comprehensive loss"
       }
      }
     },
     "localname": "ComprehensiveIncomeNetOfTax",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ConcentrationRiskBenchmarkDomain": {
     "auth_ref": [
      "r142",
      "r143",
      "r172",
      "r416",
      "r417",
      "r536"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The denominator in a calculation of a disclosed concentration risk percentage.",
        "label": "Concentration Risk Benchmark [Domain]"
       }
      }
     },
     "localname": "ConcentrationRiskBenchmarkDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ConcentrationRiskByBenchmarkAxis": {
     "auth_ref": [
      "r142",
      "r143",
      "r172",
      "r416",
      "r417",
      "r524",
      "r536"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by benchmark of concentration risk.",
        "label": "Concentration Risk Benchmark [Axis]"
       }
      }
     },
     "localname": "ConcentrationRiskByBenchmarkAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ConcentrationRiskByTypeAxis": {
     "auth_ref": [
      "r142",
      "r143",
      "r172",
      "r416",
      "r417",
      "r524",
      "r536"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by type of concentration risk, for example, but not limited to, asset, liability, net assets, geographic, customer, employees, supplier, lender.",
        "label": "Concentration Risk Type [Axis]"
       }
      }
     },
     "localname": "ConcentrationRiskByTypeAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ConcentrationRiskPercentage1": {
     "auth_ref": [
      "r142",
      "r143",
      "r172",
      "r416",
      "r417"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Concentration percentage"
       }
      }
     },
     "localname": "ConcentrationRiskPercentage1",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_ConcentrationRiskTypeDomain": {
     "auth_ref": [
      "r142",
      "r143",
      "r172",
      "r416",
      "r417",
      "r536"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "For an entity that discloses a concentration risk as a percentage of some financial balance or benchmark, identifies the type (for example, asset, liability, net assets, geographic, customer, employees, supplier, lender) of the concentration.",
        "label": "Concentration Risk Type [Domain]"
       }
      }
     },
     "localname": "ConcentrationRiskTypeDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ConsolidationPolicyTextBlock": {
     "auth_ref": [
      "r95",
      "r389"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Consolidation"
       }
      }
     },
     "localname": "ConsolidationPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/BasisOfPresentationPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ContractReceivablesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Contracts Receivable [Abstract]",
        "terseLabel": "Contracts Receivable [Abstract]"
       }
      }
     },
     "localname": "ContractReceivablesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ContractWithCustomerAssetNetCurrent": {
     "auth_ref": [
      "r295",
      "r297",
      "r308"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 2.0,
       "parentTag": "us-gaap_AssetsCurrent",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Contract with Customer, Asset, after Allowance for Credit Loss, Current",
        "terseLabel": "Contracts receivable"
       }
      }
     },
     "localname": "ContractWithCustomerAssetNetCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ContractWithCustomerLiability": {
     "auth_ref": [
      "r295",
      "r296",
      "r308"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.",
        "label": "Contract with Customer, Liability",
        "terseLabel": "Deferred revenue"
       }
      }
     },
     "localname": "ContractWithCustomerLiability",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ContractWithCustomerLiabilityAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Contract with Customer, Liability [Abstract]",
        "terseLabel": "Deferred Revenue [Abstract]"
       }
      }
     },
     "localname": "ContractWithCustomerLiabilityAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesDeferredRevenueDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ContractWithCustomerLiabilityCurrent": {
     "auth_ref": [
      "r295",
      "r296",
      "r308"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 7.0,
       "parentTag": "us-gaap_LiabilitiesCurrent",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable, classified as current.",
        "label": "Contract with Customer, Liability, Current",
        "verboseLabel": "Current portion of deferred contract revenue"
       }
      }
     },
     "localname": "ContractWithCustomerLiabilityCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ContractWithCustomerLiabilityNoncurrent": {
     "auth_ref": [
      "r295",
      "r296",
      "r308"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 2.0,
       "parentTag": "us-gaap_Liabilities",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable, classified as noncurrent.",
        "label": "Contract with Customer, Liability, Noncurrent",
        "verboseLabel": "Long-term deferred contract revenue"
       }
      }
     },
     "localname": "ContractWithCustomerLiabilityNoncurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ContractWithCustomerLiabilityRevenueRecognized": {
     "auth_ref": [
      "r309"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Contract with Customer, Liability, Revenue Recognized",
        "terseLabel": "Revenue recognized from amounts in beginning deferred revenue balance"
       }
      }
     },
     "localname": "ContractWithCustomerLiabilityRevenueRecognized",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesDeferredRevenueDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ConvertibleDebtNoncurrent": {
     "auth_ref": [
      "r37"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 3.0,
       "parentTag": "us-gaap_Liabilities",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Convertible Debt, Noncurrent",
        "terseLabel": "Convertible senior notes, net"
       }
      }
     },
     "localname": "ConvertibleDebtNoncurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ConvertibleDebtTableTextBlock": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of convertible debt instrument. Includes, but is not limited to, principal amount and amortized premium or discount.",
        "label": "Convertible Debt [Table Text Block]",
        "terseLabel": "Convertible Senior Notes"
       }
      }
     },
     "localname": "ConvertibleDebtTableTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Convertible Notes Payable [Abstract]",
        "terseLabel": "Convertible Debt [Abstract]"
       }
      }
     },
     "localname": "ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_CorporateDebtSecuritiesMember": {
     "auth_ref": [
      "r320",
      "r327",
      "r523"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Debt securities issued by domestic or foreign corporate business, banks and other entities with a promise of repayment.",
        "label": "Corporate Debt Securities [Member]",
        "terseLabel": "Corporate Debt Securities [Member]"
       }
      }
     },
     "localname": "CorporateDebtSecuritiesMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CostOfGoodsAndServicesSold": {
     "auth_ref": [
      "r68",
      "r478"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 1.0,
       "parentTag": "us-gaap_CostsAndExpenses",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Cost of Goods and Services Sold",
        "terseLabel": "Cost of sales"
       }
      }
     },
     "localname": "CostOfGoodsAndServicesSold",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CostOfSalesMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Primary financial statement caption encompassing cost of sales.",
        "label": "Cost of Sales [Member]",
        "terseLabel": "Cost of Sales [Member]"
       }
      }
     },
     "localname": "CostOfSalesMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CostOfSalesPolicyTextBlock": {
     "auth_ref": [
      "r318"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for cost of product sold and service rendered.",
        "label": "Cost of Goods and Service [Policy Text Block]",
        "terseLabel": "Cost of Sales"
       }
      }
     },
     "localname": "CostOfSalesPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_CostsAndExpenses": {
     "auth_ref": [
      "r67"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 3.0,
       "parentTag": "us-gaap_OperatingIncomeLoss",
       "weight": -1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Total costs of sales and operating expenses for the period.",
        "label": "Costs and Expenses",
        "totalLabel": "Total operating expenses"
       }
      }
     },
     "localname": "CostsAndExpenses",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_CostsAndExpensesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Costs and Expenses [Abstract]",
        "terseLabel": "Expenses:"
       }
      }
     },
     "localname": "CostsAndExpensesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_CreditConcentrationRiskMember": {
     "auth_ref": [
      "r418"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Reflects the percentage that a specified receivable or amount at risk from a counterparty under a contractual arrangement is to a specified benchmark, such as total receivables, net revenues, pretax results. Risk is the materially adverse effects of loss attributable to (a) the failure to collect a significant receivable from a major customer or group of homogeneous accounts, or (b) a failure by a counterparty to perform under terms of a contractual arrangement.",
        "label": "Credit Concentration [Member]"
       }
      }
     },
     "localname": "CreditConcentrationRiskMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_CustomerConcentrationRiskMember": {
     "auth_ref": [
      "r141",
      "r172"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Reflects the percentage that revenues in the period from one or more significant customers is to net revenues, as defined by the entity, such as total net revenues, product line revenues, segment revenues. The risk is the materially adverse effects of loss of a significant customer.",
        "label": "Customer Concentration Risk [Member]",
        "terseLabel": "Strategic Partner [Member]"
       }
      }
     },
     "localname": "CustomerConcentrationRiskMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_DebtDisclosureAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Convertible Debt [Abstract]"
       }
      }
     },
     "localname": "DebtDisclosureAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_DebtDisclosureTextBlock": {
     "auth_ref": [
      "r100",
      "r255",
      "r256",
      "r257",
      "r258",
      "r259",
      "r260",
      "r261",
      "r266",
      "r273",
      "r274",
      "r276",
      "r286"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The entire disclosure for information about short-term and long-term debt arrangements, which includes amounts of borrowings under each line of credit, note payable, commercial paper issue, bonds indenture, debenture issue, own-share lending arrangements and any other contractual agreement to repay funds, and about the underlying arrangements, rationale for a classification as long-term, including repayment terms, interest rates, collateral provided, restrictions on use of assets and activities, whether or not in compliance with debt covenants, and other matters important to users of the financial statements, such as the effects of refinancing and noncompliance with debt covenants.",
        "label": "Debt Disclosure [Text Block]",
        "terseLabel": "Convertible Debt"
       }
      }
     },
     "localname": "DebtDisclosureTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebt"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_DebtInstrumentAxis": {
     "auth_ref": [
      "r12",
      "r14",
      "r15",
      "r101",
      "r107",
      "r249",
      "r250",
      "r251",
      "r252",
      "r253",
      "r254",
      "r256",
      "r262",
      "r263",
      "r264",
      "r265",
      "r267",
      "r268",
      "r269",
      "r270",
      "r271",
      "r272",
      "r280",
      "r281",
      "r282",
      "r283",
      "r434",
      "r482",
      "r484",
      "r496"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by type of debt instrument, including, but not limited to, draws against credit facilities.",
        "label": "Debt Instrument [Axis]"
       }
      }
     },
     "localname": "DebtInstrumentAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical",
      "http://ionispharma.com/role/ConvertibleDebtDetails",
      "http://ionispharma.com/role/ConvertibleDebtTables",
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_DebtInstrumentCarryingAmount": {
     "auth_ref": [
      "r15",
      "r277",
      "r484",
      "r496"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Outstanding principal balance"
       }
      }
     },
     "localname": "DebtInstrumentCarryingAmount",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DebtInstrumentConvertibleConversionPrice1": {
     "auth_ref": [
      "r251",
      "r278"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The price per share of the conversion feature embedded in the debt instrument.",
        "label": "Conversion price per share (in dollars per share)"
       }
      }
     },
     "localname": "DebtInstrumentConvertibleConversionPrice1",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "perShareItemType"
    },
    "us-gaap_DebtInstrumentFaceAmount": {
     "auth_ref": [
      "r249",
      "r280",
      "r281",
      "r432",
      "r434",
      "r435"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Face (par) amount of debt instrument at time of issuance.",
        "label": "Debt Instrument, Face Amount",
        "verboseLabel": "Face amount of offering"
       }
      }
     },
     "localname": "DebtInstrumentFaceAmount",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DebtInstrumentInterestRateEffectivePercentage": {
     "auth_ref": [
      "r35",
      "r279",
      "r432",
      "r434"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Effective interest rate for the funds borrowed under the debt agreement considering interest compounding and original issue discount or premium.",
        "label": "Debt Instrument, Interest Rate, Effective Percentage",
        "terseLabel": "Effective interest rate"
       }
      }
     },
     "localname": "DebtInstrumentInterestRateEffectivePercentage",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_DebtInstrumentInterestRateStatedPercentage": {
     "auth_ref": [
      "r35",
      "r250"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Contractual interest rate for funds borrowed, under the debt agreement.",
        "label": "Interest rate",
        "terseLabel": "Interest rate on convertible senior notes"
       }
      }
     },
     "localname": "DebtInstrumentInterestRateStatedPercentage",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical",
      "http://ionispharma.com/role/ConvertibleDebtDetails",
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_DebtInstrumentLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Debt Instrument [Line Items]"
       }
      }
     },
     "localname": "DebtInstrumentLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_DebtInstrumentMaturityDate": {
     "auth_ref": [
      "r36",
      "r252",
      "r411"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Date when the debt instrument is scheduled to be fully repaid, in YYYY-MM-DD format.",
        "label": "Maturity date"
       }
      }
     },
     "localname": "DebtInstrumentMaturityDate",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "dateItemType"
    },
    "us-gaap_DebtInstrumentNameDomain": {
     "auth_ref": [
      "r37",
      "r101",
      "r107",
      "r249",
      "r250",
      "r251",
      "r252",
      "r253",
      "r254",
      "r256",
      "r262",
      "r263",
      "r264",
      "r265",
      "r267",
      "r268",
      "r269",
      "r270",
      "r271",
      "r272",
      "r280",
      "r281",
      "r282",
      "r283",
      "r434"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The name for the particular debt instrument or borrowing that distinguishes it from other debt instruments or borrowings, including draws against credit facilities.",
        "label": "Debt Instrument, Name [Domain]"
       }
      }
     },
     "localname": "DebtInstrumentNameDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical",
      "http://ionispharma.com/role/ConvertibleDebtDetails",
      "http://ionispharma.com/role/ConvertibleDebtTables",
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_DebtInstrumentRepurchasedFaceAmount": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Face (par) amount of the original debt instrument that was repurchased.",
        "label": "Principal amount repurchased"
       }
      }
     },
     "localname": "DebtInstrumentRepurchasedFaceAmount",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DebtInstrumentTable": {
     "auth_ref": [
      "r37",
      "r101",
      "r107",
      "r249",
      "r250",
      "r251",
      "r252",
      "r253",
      "r254",
      "r256",
      "r262",
      "r263",
      "r264",
      "r265",
      "r267",
      "r268",
      "r269",
      "r270",
      "r271",
      "r272",
      "r275",
      "r280",
      "r281",
      "r282",
      "r283",
      "r290",
      "r291",
      "r292",
      "r293",
      "r431",
      "r432",
      "r434",
      "r435",
      "r495"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "A table or schedule providing information pertaining to long-term debt instruments or arrangements, including identification, terms, features, collateral requirements and other information necessary to a fair presentation. These are debt arrangements that originally required repayment more than twelve months after issuance or greater than the normal operating cycle of the company, if longer.",
        "label": "Schedule of Long-term Debt Instruments [Table]"
       }
      }
     },
     "localname": "DebtInstrumentTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_DebtPolicyTextBlock": {
     "auth_ref": [
      "r237"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Debt, Policy [Policy Text Block]",
        "terseLabel": "Convertible Debt"
       }
      }
     },
     "localname": "DebtPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger": {
     "auth_ref": [
      "r194",
      "r218",
      "r221"
     ],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for more than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.",
        "label": "Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, 12 Months or Longer",
        "terseLabel": "More than 12 months of temporary impairment"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss": {
     "auth_ref": [
      "r194",
      "r218"
     ],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for 12 months or longer, without allowance for credit loss. Includes beneficial interest in securitized financial asset.",
        "label": "Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, 12 Months or Longer, Accumulated Loss",
        "negatedLabel": "More than 12 months of temporary impairment"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months": {
     "auth_ref": [
      "r194",
      "r218",
      "r221"
     ],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": 0.0,
       "parentTag": "us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.",
        "label": "Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, Less than 12 Months",
        "terseLabel": "Less than 12 months of temporary impairment"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss": {
     "auth_ref": [
      "r194",
      "r218"
     ],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": 0.0,
       "parentTag": "us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.",
        "label": "Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, Less than 12 Months, Accumulated Loss",
        "negatedLabel": "Less than 12 months of temporary impairment"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions": {
     "auth_ref": [
      "r216"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Number of investments in debt securities measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without an allowance for credit loss. Includes beneficial interest in securitized financial asset.",
        "label": "Debt Securities, Available-for-sale, Continuous Unrealized Loss Position, Less than 12 Months, Number of Positions",
        "terseLabel": "Number of investments"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition": {
     "auth_ref": [
      "r191",
      "r214",
      "r221"
     ],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in unrealized loss position without allowance for credit loss.",
        "label": "Debt Securities, Available-for-sale, Unrealized Loss Position",
        "totalLabel": "Total temporary impairment"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleUnrealizedLossPosition",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss": {
     "auth_ref": [
      "r192",
      "r215"
     ],
     "calculation": {
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in unrealized loss position, without allowance for credit loss. Includes beneficial interest in securitized financial asset.",
        "label": "Debt Securities, Available-for-sale, Unrealized Loss Position, Accumulated Loss",
        "negatedTotalLabel": "Total temporary impairment"
       }
      }
     },
     "localname": "DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DebtSecuritiesMember": {
     "auth_ref": [
      "r195"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Debt instrument issued by corporations, governments and governmental agencies, municipalities, and other institutions.",
        "label": "Debt Securities [Member]",
        "terseLabel": "Available-for-sale Securities [Member]"
       }
      }
     },
     "localname": "DebtSecuritiesMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_DeferredFinanceCostsNet": {
     "auth_ref": [
      "r29",
      "r262",
      "r433"
     ],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount, after accumulated amortization, of debt issuance costs. Includes, but is not limited to, legal, accounting, underwriting, printing, and registration costs.",
        "label": "Debt Issuance Costs, Net",
        "terseLabel": "Unamortized debt issuance costs"
       }
      }
     },
     "localname": "DeferredFinanceCostsNet",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_Depreciation": {
     "auth_ref": [
      "r89",
      "r231"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 1.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Depreciation",
        "terseLabel": "Depreciation"
       }
      }
     },
     "localname": "Depreciation",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_DerivativesPolicyTextBlock": {
     "auth_ref": [
      "r106",
      "r396",
      "r397",
      "r398",
      "r399",
      "r402"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for its derivative instruments and hedging activities.",
        "label": "Derivatives, Policy [Policy Text Block]",
        "terseLabel": "Call Spread"
       }
      }
     },
     "localname": "DerivativesPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_DisaggregationOfRevenueLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Disaggregation of Revenue [Line Items]"
       }
      }
     },
     "localname": "DisaggregationOfRevenueLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_DisaggregationOfRevenueTable": {
     "auth_ref": [
      "r307",
      "r310",
      "r311",
      "r312",
      "r313",
      "r314",
      "r315",
      "r316"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of information about disaggregation of revenue into categories depicting how nature, amount, timing, and uncertainty of revenue and cash flows are affected by economic factor.",
        "label": "Disaggregation of Revenue [Table]"
       }
      }
     },
     "localname": "DisaggregationOfRevenueTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EarningsPerShareBasic": {
     "auth_ref": [
      "r65",
      "r114",
      "r115",
      "r116",
      "r117",
      "r118",
      "r122",
      "r124",
      "r127",
      "r128",
      "r129",
      "r132",
      "r133",
      "r405",
      "r406",
      "r490",
      "r507"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.",
        "label": "Basic net loss per share (in dollars per share)"
       }
      }
     },
     "localname": "EarningsPerShareBasic",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails"
     ],
     "xbrltype": "perShareItemType"
    },
    "us-gaap_EarningsPerShareBasicAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Basic Net Loss per Share [Abstract]"
       }
      }
     },
     "localname": "EarningsPerShareBasicAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EarningsPerShareBasicLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]"
       }
      }
     },
     "localname": "EarningsPerShareBasicLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EarningsPerShareDiluted": {
     "auth_ref": [
      "r65",
      "r114",
      "r115",
      "r116",
      "r117",
      "r118",
      "r124",
      "r127",
      "r128",
      "r129",
      "r132",
      "r133",
      "r405",
      "r406",
      "r490",
      "r507"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Diluted net loss per share (in dollars per share)"
       }
      }
     },
     "localname": "EarningsPerShareDiluted",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "perShareItemType"
    },
    "us-gaap_EarningsPerSharePolicyTextBlock": {
     "auth_ref": [
      "r130",
      "r131"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Earnings Per Share, Policy [Policy Text Block]",
        "terseLabel": "Basic and Diluted Net Loss per Share"
       }
      }
     },
     "localname": "EarningsPerSharePolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_EffectOfExchangeRateOnCashAndCashEquivalents": {
     "auth_ref": [
      "r422"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 4.0,
       "parentTag": "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of increase (decrease) from the effect of exchange rate changes on cash and cash equivalent balances held in foreign currencies.",
        "label": "Effect of Exchange Rate on Cash and Cash Equivalents",
        "terseLabel": "Effects of exchange rates on cash"
       }
      }
     },
     "localname": "EffectOfExchangeRateOnCashAndCashEquivalents",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EmployeeRelatedLiabilitiesCurrent": {
     "auth_ref": [
      "r33"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 1.0,
       "parentTag": "us-gaap_LiabilitiesCurrent",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Employee-related Liabilities, Current",
        "terseLabel": "Accrued compensation"
       }
      }
     },
     "localname": "EmployeeRelatedLiabilitiesCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]"
       }
      }
     },
     "localname": "EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Unrecognized Compensation Expense [Abstract]"
       }
      }
     },
     "localname": "EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1": {
     "auth_ref": [
      "r349"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Share-based Payment Arrangement, Nonvested Award, Cost Not yet Recognized, Period for Recognition",
        "terseLabel": "Weighted average period for recognition"
       }
      }
     },
     "localname": "EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions": {
     "auth_ref": [
      "r349"
     ],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of cost to be recognized for nonvested award under share-based payment arrangement. Excludes share and unit options.",
        "label": "Share-based Payment Arrangement, Nonvested Award, Excluding Option, Cost Not yet Recognized, Amount",
        "terseLabel": "Unrecognized compensation cost related to non-vested units"
       }
      }
     },
     "localname": "EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions": {
     "auth_ref": [
      "r349"
     ],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of cost to be recognized for option under share-based payment arrangement.",
        "label": "Share-based Payment Arrangement, Nonvested Award, Option, Cost Not yet Recognized, Amount",
        "terseLabel": "Unrecognized compensation expense related to non-vested stock options"
       }
      }
     },
     "localname": "EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EmployeeStockMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "An Employee Stock Purchase Plan is a tax-efficient means by which employees of a corporation can purchase the corporation's stock.",
        "label": "Employee Stock [Member]",
        "terseLabel": "ESPP [Member]"
       }
      }
     },
     "localname": "EmployeeStockMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_EmployeeStockOptionMember": {
     "auth_ref": [
      "r346"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Share-based payment arrangement granting right, subject to vesting and other restrictions, to purchase or sell certain number of shares at predetermined price for specified period of time.",
        "label": "Share-based Payment Arrangement, Option [Member]",
        "terseLabel": "Stock Options [Member]"
       }
      }
     },
     "localname": "EmployeeStockOptionMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_EntityWideRevenueMajorCustomerLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Revenue, Major Customer [Line Items]"
       }
      }
     },
     "localname": "EntityWideRevenueMajorCustomerLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_EquityComponentDomain": {
     "auth_ref": [
      "r0",
      "r58",
      "r59",
      "r60",
      "r109",
      "r110",
      "r111",
      "r113",
      "r119",
      "r121",
      "r135",
      "r206",
      "r289",
      "r294",
      "r352",
      "r353",
      "r354",
      "r370",
      "r371",
      "r404",
      "r424",
      "r425",
      "r426",
      "r427",
      "r428",
      "r429",
      "r517",
      "r518",
      "r519",
      "r552"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Components of equity are the parts of the total Equity balance including that which is allocated to common, preferred, treasury stock, retained earnings, etc.",
        "label": "Equity Component [Domain]"
       }
      }
     },
     "localname": "EquityComponentDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_EquitySecuritiesFvNi": {
     "auth_ref": [
      "r415"
     ],
     "calculation": {
      "http://ionispharma.com/role/FairValueMeasurementsDetails": {
       "order": 2.0,
       "parentTag": "us-gaap_AssetsFairValueDisclosure",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), classified as current.",
        "label": "Equity Securities, FV-NI, Current",
        "terseLabel": "Investment",
        "verboseLabel": "Estimated fair value"
       }
      }
     },
     "localname": "EquitySecuritiesFvNi",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EquitySecuritiesFvNiCost": {
     "auth_ref": [],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Equity Securities, FV-NI, Cost",
        "terseLabel": "Amortized cost"
       }
      }
     },
     "localname": "EquitySecuritiesFvNiCost",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EquitySecuritiesFvNiUnrealizedGain": {
     "auth_ref": [
      "r199"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).",
        "label": "Equity Securities, FV-NI, Unrealized Gain",
        "terseLabel": "Gross unrealized gains"
       }
      }
     },
     "localname": "EquitySecuritiesFvNiUnrealizedGain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EquitySecuritiesFvNiUnrealizedLoss": {
     "auth_ref": [
      "r199"
     ],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).",
        "label": "Equity Securities, FV-NI, Unrealized Loss",
        "negatedLabel": "Gross unrealized losses"
       }
      }
     },
     "localname": "EquitySecuritiesFvNiUnrealizedLoss",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_EquitySecuritiesMember": {
     "auth_ref": [
      "r9",
      "r13",
      "r195",
      "r497",
      "r533",
      "r534",
      "r535"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Ownership interest or right to acquire or dispose of ownership interest in corporations and other legal entities for which ownership interest is represented by shares of common or preferred stock, convertible securities, stock rights, or stock warrants.",
        "label": "Equity Securities [Member]",
        "terseLabel": "Equity Securities [Member]"
       }
      }
     },
     "localname": "EquitySecuritiesMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]",
        "terseLabel": "Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]"
       }
      }
     },
     "localname": "FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable": {
     "auth_ref": [
      "r407",
      "r408",
      "r409",
      "r413"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of information about asset and liability measured at fair value on recurring and nonrecurring basis.",
        "label": "Fair Value Measurements, Recurring and Nonrecurring [Table]"
       }
      }
     },
     "localname": "FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FairValueAssetsMeasuredOnRecurringBasisTextBlock": {
     "auth_ref": [
      "r407",
      "r408"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of assets, including [financial] instruments measured at fair value that are classified in stockholders' equity, if any, by class that are measured at fair value on a recurring basis. The disclosures contemplated herein include the fair value measurements at the reporting date by the level within the fair value hierarchy in which the fair value measurements in their entirety fall, segregating fair value measurements using quoted prices in active markets for identical assets (Level 1), significant other observable inputs (Level 2), and significant unobservable inputs (Level 3).",
        "label": "Fair Value, Assets Measured on Recurring Basis [Table Text Block]",
        "terseLabel": "Assets Measured at Fair Value on a Recurring Basis"
       }
      }
     },
     "localname": "FairValueAssetsMeasuredOnRecurringBasisTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_FairValueByFairValueHierarchyLevelAxis": {
     "auth_ref": [
      "r264",
      "r280",
      "r281",
      "r320",
      "r321",
      "r322",
      "r323",
      "r324",
      "r325",
      "r326",
      "r327",
      "r408",
      "r445",
      "r446",
      "r447"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by level within fair value hierarchy and fair value measured at net asset value per share as practical expedient.",
        "label": "Fair Value, Hierarchy [Axis]"
       }
      }
     },
     "localname": "FairValueByFairValueHierarchyLevelAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FairValueByMeasurementFrequencyAxis": {
     "auth_ref": [
      "r407",
      "r408",
      "r410",
      "r411",
      "r414"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by measurement frequency.",
        "label": "Measurement Frequency [Axis]"
       }
      }
     },
     "localname": "FairValueByMeasurementFrequencyAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FairValueDisclosuresAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Fair Value Measurements [Abstract]"
       }
      }
     },
     "localname": "FairValueDisclosuresAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_FairValueDisclosuresTextBlock": {
     "auth_ref": [
      "r412"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The entire disclosure for the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired information.",
        "label": "Fair Value Disclosures [Text Block]",
        "terseLabel": "Fair Value Measurements"
       }
      }
     },
     "localname": "FairValueDisclosuresTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurements"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_FairValueInputsLevel1Member": {
     "auth_ref": [
      "r264",
      "r320",
      "r321",
      "r326",
      "r327",
      "r408",
      "r445"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Quoted prices in active markets for identical assets or liabilities that the reporting entity can access at the measurement date.",
        "label": "Fair Value, Inputs, Level 1 [Member]",
        "terseLabel": "Quoted Prices in Active Markets (Level 1) [Member]"
       }
      }
     },
     "localname": "FairValueInputsLevel1Member",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueInputsLevel2Member": {
     "auth_ref": [
      "r264",
      "r280",
      "r281",
      "r320",
      "r321",
      "r326",
      "r327",
      "r408",
      "r446"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Inputs other than quoted prices included within level 1 that are observable for an asset or liability, either directly or indirectly, including, but not limited to, quoted prices for similar assets or liabilities in active markets, or quoted prices for identical or similar assets or liabilities in inactive markets.",
        "label": "Fair Value, Inputs, Level 2 [Member]",
        "terseLabel": "Significant Other Observable Inputs (Level 2) [Member]"
       }
      }
     },
     "localname": "FairValueInputsLevel2Member",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueInputsLevel3Member": {
     "auth_ref": [
      "r264",
      "r280",
      "r281",
      "r320",
      "r321",
      "r322",
      "r323",
      "r324",
      "r325",
      "r326",
      "r327",
      "r408",
      "r447"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Unobservable inputs that reflect the entity's own assumption about the assumptions market participants would use in pricing.",
        "label": "Fair Value, Inputs, Level 3 [Member]",
        "terseLabel": "Significant Unobservable Inputs (Level 3) [Member]"
       }
      }
     },
     "localname": "FairValueInputsLevel3Member",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueMeasurementFrequencyDomain": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Measurement frequency.",
        "label": "Fair Value, Measurement Frequency [Domain]"
       }
      }
     },
     "localname": "FairValueMeasurementFrequencyDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueMeasurementsFairValueHierarchyDomain": {
     "auth_ref": [
      "r264",
      "r280",
      "r281",
      "r320",
      "r321",
      "r322",
      "r323",
      "r324",
      "r325",
      "r326",
      "r327",
      "r445",
      "r446",
      "r447"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Categories used to prioritize the inputs to valuation techniques to measure fair value.",
        "label": "Fair Value Hierarchy [Domain]"
       }
      }
     },
     "localname": "FairValueMeasurementsFairValueHierarchyDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueMeasurementsRecurringMember": {
     "auth_ref": [
      "r412",
      "r414"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Frequent fair value measurement. Includes, but is not limited to, fair value adjustment for impairment of asset, liability or equity, frequently measured at fair value.",
        "label": "Fair Value, Recurring [Member]",
        "terseLabel": "Recurring Basis [Member]"
       }
      }
     },
     "localname": "FairValueMeasurementsRecurringMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_FairValueNetAssetLiabilityAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Fair Value, Net Asset (Liability) [Abstract]",
        "terseLabel": "Fair Value Measurements [Abstract]"
       }
      }
     },
     "localname": "FairValueNetAssetLiabilityAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FinancialInstrumentAxis": {
     "auth_ref": [
      "r188",
      "r189",
      "r196",
      "r197",
      "r198",
      "r207",
      "r208",
      "r209",
      "r210",
      "r211",
      "r217",
      "r219",
      "r220",
      "r221",
      "r275",
      "r288",
      "r403",
      "r442",
      "r443",
      "r444",
      "r445",
      "r446",
      "r447",
      "r448",
      "r449",
      "r450",
      "r451",
      "r452",
      "r453",
      "r454",
      "r455",
      "r456",
      "r457",
      "r458",
      "r459",
      "r460",
      "r461",
      "r462",
      "r463",
      "r464",
      "r465",
      "r466",
      "r467",
      "r468",
      "r469",
      "r470",
      "r471",
      "r544",
      "r545",
      "r546",
      "r547",
      "r548",
      "r549",
      "r550"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by type of financial instrument.",
        "label": "Financial Instrument [Axis]"
       }
      }
     },
     "localname": "FinancialInstrumentAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_FiniteLivedIntangibleAssetsNet": {
     "auth_ref": [
      "r227",
      "r479"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 4.0,
       "parentTag": "us-gaap_Assets",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount after amortization of assets, excluding financial assets and goodwill, lacking physical substance with a finite life.",
        "label": "Finite-Lived Intangible Assets, Net",
        "terseLabel": "Patents, net"
       }
      }
     },
     "localname": "FiniteLivedIntangibleAssetsNet",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_GainLossOnDispositionOfAssets": {
     "auth_ref": [
      "r89",
      "r230",
      "r234"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 14.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of gain (loss) on sale or disposal of property, plant and equipment assets, excluding oil and gas property and timber property.",
        "label": "Gain (Loss) on Disposition of Property Plant Equipment, Excluding Oil and Gas Property and Timber Property",
        "negatedLabel": "Non-cash losses related to disposal of property, plant and equipment"
       }
      }
     },
     "localname": "GainLossOnDispositionOfAssets",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_GainLossOnInvestments": {
     "auth_ref": [
      "r71",
      "r89",
      "r183"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 8.0,
       "parentTag": "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of realized and unrealized gain (loss) on investment.",
        "label": "Gain (Loss) on Investments",
        "terseLabel": "Gain on investments",
        "verboseLabel": "Loss on investments"
       }
      }
     },
     "localname": "GainLossOnInvestments",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_GainsLossesOnExtinguishmentOfDebt": {
     "auth_ref": [
      "r89",
      "r284",
      "r285"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Difference between the fair value of payments made and the carrying amount of debt which is extinguished prior to maturity.",
        "label": "Gain (Loss) on Extinguishment of Debt",
        "terseLabel": "Loss on early retirement of debt"
       }
      }
     },
     "localname": "GainsLossesOnExtinguishmentOfDebt",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_GranteeStatusAxis": {
     "auth_ref": [
      "r330",
      "r332",
      "r346"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by status of recipient to whom award is granted.",
        "label": "Grantee Status [Axis]"
       }
      }
     },
     "localname": "GranteeStatusAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_GranteeStatusDomain": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Status of recipient to whom award is granted.",
        "label": "Grantee Status [Domain]"
       }
      }
     },
     "localname": "GranteeStatusDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ImpairmentOfIntangibleAssetsFinitelived": {
     "auth_ref": [
      "r89",
      "r229"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 15.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Impairment of Intangible Assets, Finite-lived",
        "terseLabel": "Non-cash losses related to patents"
       }
      }
     },
     "localname": "ImpairmentOfIntangibleAssetsFinitelived",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for the impairment and disposal of long-lived assets including goodwill and other intangible assets.",
        "label": "Impairment or Disposal of Long-Lived Assets, Including Intangible Assets, Policy [Policy Text Block]",
        "terseLabel": "Long-Lived Assets"
       }
      }
     },
     "localname": "ImpairmentOrDisposalOfLongLivedAssetsIncludingIntangibleAssetsPolicyPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest": {
     "auth_ref": [
      "r62",
      "r153",
      "r161",
      "r164",
      "r167",
      "r169",
      "r480",
      "r487",
      "r492",
      "r509"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 0.0,
       "parentTag": "us-gaap_NetIncomeLoss",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.",
        "label": "Income (Loss) from Continuing Operations before Income Taxes, Noncontrolling Interest",
        "totalLabel": "Loss before income tax expense"
       }
      }
     },
     "localname": "IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncomeStatementAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "CONSOLIDATED STATEMENTS OF OPERATIONS [Abstract]"
       }
      }
     },
     "localname": "IncomeStatementAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_IncomeStatementLocationAxis": {
     "auth_ref": [
      "r235",
      "r236"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by location in the income statement.",
        "label": "Income Statement Location [Axis]"
       }
      }
     },
     "localname": "IncomeStatementLocationAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_IncomeStatementLocationDomain": {
     "auth_ref": [
      "r236"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Location in the income statement.",
        "label": "Income Statement Location [Domain]"
       }
      }
     },
     "localname": "IncomeStatementLocationDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_IncomeTaxDisclosureAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Income Taxes [Abstract]"
       }
      }
     },
     "localname": "IncomeTaxDisclosureAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_IncomeTaxDisclosureTextBlock": {
     "auth_ref": [
      "r103",
      "r364",
      "r365",
      "r368",
      "r372",
      "r374",
      "r376",
      "r377",
      "r378"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The entire disclosure for income taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.",
        "label": "Income Tax Disclosure [Text Block]",
        "verboseLabel": "Income Taxes"
       }
      }
     },
     "localname": "IncomeTaxDisclosureTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/IncomeTaxes"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_IncomeTaxExpenseBenefit": {
     "auth_ref": [
      "r104",
      "r120",
      "r121",
      "r152",
      "r363",
      "r373",
      "r375",
      "r510"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 1.0,
       "parentTag": "us-gaap_NetIncomeLoss",
       "weight": -1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.",
        "label": "Income Tax Expense (Benefit)",
        "negatedTerseLabel": "Income tax expense",
        "terseLabel": "Income tax expense"
       }
      }
     },
     "localname": "IncomeTaxExpenseBenefit",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
      "http://ionispharma.com/role/IncomeTaxesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncomeTaxPolicyTextBlock": {
     "auth_ref": [
      "r57",
      "r361",
      "r362",
      "r365",
      "r366",
      "r367",
      "r369"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Income Tax, Policy [Policy Text Block]",
        "terseLabel": "Income Taxes"
       }
      }
     },
     "localname": "IncomeTaxPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_IncomeTaxesPaid": {
     "auth_ref": [
      "r85",
      "r92"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The amount of cash paid during the current period to foreign, federal, state, and local authorities as taxes on income.",
        "label": "Income Taxes Paid",
        "terseLabel": "Income taxes paid"
       }
      }
     },
     "localname": "IncomeTaxesPaid",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInAccountsPayable": {
     "auth_ref": [
      "r88"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 22.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Increase (Decrease) in Accounts Payable",
        "terseLabel": "Accounts payable"
       }
      }
     },
     "localname": "IncreaseDecreaseInAccountsPayable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable": {
     "auth_ref": [
      "r88"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 21.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Increase (Decrease) in Income Taxes Payable",
        "terseLabel": "Income taxes receivable"
       }
      }
     },
     "localname": "IncreaseDecreaseInAccruedIncomeTaxesPayable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInContractWithCustomerAsset": {
     "auth_ref": [
      "r88"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 18.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Increase (Decrease) in Contract with Customer, Asset",
        "negatedLabel": "Contracts receivable"
       }
      }
     },
     "localname": "IncreaseDecreaseInContractWithCustomerAsset",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInContractWithCustomerLiability": {
     "auth_ref": [
      "r88",
      "r473"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 25.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of increase (decrease) in obligation to transfer good or service to customer for which consideration has been received or is receivable.",
        "label": "Increase (Decrease) in Contract with Customer, Liability",
        "terseLabel": "Deferred contract revenue"
       }
      }
     },
     "localname": "IncreaseDecreaseInContractWithCustomerLiability",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInInventories": {
     "auth_ref": [
      "r88"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 19.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Increase (Decrease) in Inventories",
        "negatedLabel": "Inventories"
       }
      }
     },
     "localname": "IncreaseDecreaseInInventories",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInOperatingCapitalAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Increase (Decrease) in Operating Capital [Abstract]",
        "terseLabel": "Changes in operating assets and liabilities:"
       }
      }
     },
     "localname": "IncreaseDecreaseInOperatingCapitalAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_IncreaseDecreaseInOtherCurrentLiabilities": {
     "auth_ref": [
      "r88"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 24.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of increase (decrease) in current liabilities classified as other.",
        "label": "Increase (Decrease) in Other Current Liabilities",
        "terseLabel": "Accrued liabilities and other current liabilities"
       }
      }
     },
     "localname": "IncreaseDecreaseInOtherCurrentLiabilities",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities": {
     "auth_ref": [
      "r88"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 23.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of increase (decrease) in employer-related costs classified as other and current.",
        "label": "Increase (Decrease) in Other Employee-Related Liabilities",
        "terseLabel": "Accrued compensation"
       }
      }
     },
     "localname": "IncreaseDecreaseInOtherEmployeeRelatedLiabilities",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInOtherOperatingAssets": {
     "auth_ref": [
      "r88"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 20.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of increase (decrease) in operating assets classified as other.",
        "label": "Increase (Decrease) in Other Operating Assets",
        "negatedLabel": "Other current and long-term assets"
       }
      }
     },
     "localname": "IncreaseDecreaseInOtherOperatingAssets",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_IncreaseDecreaseInStockholdersEquityRollForward": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.",
        "label": "Increase (Decrease) in Stockholders' Equity [Roll Forward]",
        "terseLabel": "Increase (Decrease) in Stockholders' Equity [Roll Forward]"
       }
      }
     },
     "localname": "IncreaseDecreaseInStockholdersEquityRollForward",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_IntangibleAssetsFiniteLivedPolicy": {
     "auth_ref": [
      "r96",
      "r226",
      "r475",
      "r476",
      "r477",
      "r479"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Intangible Assets, Finite-Lived, Policy [Policy Text Block]",
        "terseLabel": "Patent Expenses"
       }
      }
     },
     "localname": "IntangibleAssetsFiniteLivedPolicy",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_InterestExpense": {
     "auth_ref": [
      "r61",
      "r151",
      "r430",
      "r433",
      "r491"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 4.0,
       "parentTag": "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest",
       "weight": -1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of the cost of borrowed funds accounted for as interest expense.",
        "label": "Interest Expense",
        "negatedLabel": "Interest expense"
       }
      }
     },
     "localname": "InterestExpense",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InterestPaidNet": {
     "auth_ref": [
      "r82",
      "r84",
      "r92"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Interest Paid, Excluding Capitalized Interest, Operating Activities",
        "terseLabel": "Interest paid"
       }
      }
     },
     "localname": "InterestPaidNet",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InventoryCurrentTable": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of information about inventory expected to be sold or consumed within one year or operating cycle, if longer.",
        "label": "Inventory, Current [Table]"
       }
      }
     },
     "localname": "InventoryCurrentTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InventoryFinishedGoods": {
     "auth_ref": [
      "r39"
     ],
     "calculation": {
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails": {
       "order": 2.0,
       "parentTag": "us-gaap_InventoryNet",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount before valuation and LIFO reserves of completed merchandise or goods expected to be sold within one year or operating cycle, if longer.",
        "label": "Inventory, Finished Goods, Gross",
        "terseLabel": "Finished goods"
       }
      }
     },
     "localname": "InventoryFinishedGoods",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InventoryLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Inventory [Line Items]"
       }
      }
     },
     "localname": "InventoryLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InventoryNet": {
     "auth_ref": [
      "r5",
      "r42",
      "r441"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 3.0,
       "parentTag": "us-gaap_AssetsCurrent",
       "weight": 1.0
      },
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount after valuation and LIFO reserves of inventory expected to be sold, or consumed within one year or operating cycle, if longer.",
        "label": "Inventory, Net",
        "terseLabel": "Inventories",
        "totalLabel": "Total inventory"
       }
      }
     },
     "localname": "InventoryNet",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InventoryNetAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Inventory, Net [Abstract]",
        "terseLabel": "Inventory Valuation [Abstract]"
       }
      }
     },
     "localname": "InventoryNetAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InventoryPolicyTextBlock": {
     "auth_ref": [
      "r8",
      "r43",
      "r97",
      "r134",
      "r222",
      "r223",
      "r224",
      "r474"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Inventory, Policy [Policy Text Block]",
        "terseLabel": "Inventory Valuation"
       }
      }
     },
     "localname": "InventoryPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_InventoryRawMaterials": {
     "auth_ref": [
      "r41"
     ],
     "calculation": {
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails": {
       "order": 0.0,
       "parentTag": "us-gaap_InventoryNet",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount before valuation and LIFO reserves of raw materials expected to be sold, or consumed within one year or operating cycle, if longer.",
        "label": "Inventory, Raw Materials, Gross",
        "terseLabel": "Raw materials"
       }
      }
     },
     "localname": "InventoryRawMaterials",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InventoryWorkInProcess": {
     "auth_ref": [
      "r40"
     ],
     "calculation": {
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails": {
       "order": 1.0,
       "parentTag": "us-gaap_InventoryNet",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Inventory, Work in Process, Gross",
        "terseLabel": "Work in process"
       }
      }
     },
     "localname": "InventoryWorkInProcess",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InvestmentHoldingsLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Investment Holdings [Line Items]"
       }
      }
     },
     "localname": "InvestmentHoldingsLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentHoldingsTable": {
     "auth_ref": [
      "r525",
      "r530",
      "r531",
      "r532"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The investment holdings table is used for any listing of investments. The \"Investment [Axis]\" identifies the investment for which the line items apply. The other axes are used for categorizing the investments and creating useful subtotals. These axes cover different categorizations. The appropriate axes are expected to be used. Additional axes can be added for alternative categorizations.",
        "label": "Investment Holdings [Table]"
       }
      }
     },
     "localname": "InvestmentHoldingsTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentIncomeNet": {
     "auth_ref": [
      "r70",
      "r72"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 3.0,
       "parentTag": "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount after accretion (amortization) of discount (premium), and investment expense, of interest income and dividend income on nonoperating securities.",
        "label": "Investment Income, Net",
        "terseLabel": "Investment income"
       }
      }
     },
     "localname": "InvestmentIncomeNet",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_InvestmentPolicyTextBlock": {
     "auth_ref": [
      "r202",
      "r508"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for investment in financial asset.",
        "label": "Investment, Policy [Policy Text Block]",
        "terseLabel": "Cash, Cash Equivalents and Investments"
       }
      }
     },
     "localname": "InvestmentPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_InvestmentSecondaryCategorizationAxis": {
     "auth_ref": [
      "r527",
      "r528",
      "r529"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by second categorization of investments, which may include, but is not limited to industry.",
        "label": "Investment Secondary Categorization [Axis]"
       }
      }
     },
     "localname": "InvestmentSecondaryCategorizationAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentTextBlock": {
     "auth_ref": [
      "r195",
      "r200",
      "r204",
      "r205"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The entire disclosure for investment.",
        "label": "Investment [Text Block]",
        "terseLabel": "Investments"
       }
      }
     },
     "localname": "InvestmentTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/Investments"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_InvestmentsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Investments [Abstract]"
       }
      }
     },
     "localname": "InvestmentsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentsAllOtherInvestmentsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Investments, All Other Investments [Abstract]",
        "terseLabel": "Ownership Interests in Private and Public Companies [Abstract]"
       }
      }
     },
     "localname": "InvestmentsAllOtherInvestmentsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_InvestmentsBySecondaryCategorizationDomain": {
     "auth_ref": [
      "r526",
      "r527",
      "r528",
      "r529"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Investments in the \"Investment Holdings [Table]\" and the \"Summary of Investment Holdings [Table]\" are often categorized at two levels. The first categorization is the investment type. The second categorization can vary. The usual secondary categorizations are industry, country or geography.",
        "label": "Investments by Secondary Categorization [Domain]"
       }
      }
     },
     "localname": "InvestmentsBySecondaryCategorizationDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of maturities of an entity's investments as well as any other information pertinent to the investments.",
        "label": "Investments Classified by Contractual Maturity Date [Table Text Block]",
        "terseLabel": "Contract Maturity of Available-for-Sale Securities"
       }
      }
     },
     "localname": "InvestmentsClassifiedByContractualMaturityDateTableTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_LesseeDisclosureAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Lessee Disclosure [Abstract]",
        "terseLabel": "Leases [Abstract]"
       }
      }
     },
     "localname": "LesseeDisclosureAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LesseeLeaseDescriptionLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Lessee, Lease, Description [Line Items]"
       }
      }
     },
     "localname": "LesseeLeaseDescriptionLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LesseeLeaseDescriptionTable": {
     "auth_ref": [
      "r437"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of information about lessee's leases.",
        "label": "Lessee, Lease, Description [Table]"
       }
      }
     },
     "localname": "LesseeLeaseDescriptionTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LesseeLeasesPolicyTextBlock": {
     "auth_ref": [
      "r436"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for leasing arrangement entered into by lessee.",
        "label": "Lessee, Leases [Policy Text Block]",
        "terseLabel": "Leases"
       }
      }
     },
     "localname": "LesseeLeasesPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue": {
     "auth_ref": [
      "r438"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of lessee's undiscounted obligation for lease payment for operating lease.",
        "label": "Lessee, Operating Lease, Liability, to be Paid",
        "terseLabel": "Lease payments over sublease term"
       }
      }
     },
     "localname": "LesseeOperatingLeaseLiabilityPaymentsDue",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_Liabilities": {
     "auth_ref": [
      "r32",
      "r102",
      "r163",
      "r203",
      "r238",
      "r239",
      "r240",
      "r242",
      "r243",
      "r244",
      "r245",
      "r246",
      "r247",
      "r248",
      "r388",
      "r392",
      "r393",
      "r419",
      "r439",
      "r440"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 1.0,
       "parentTag": "us-gaap_LiabilitiesAndStockholdersEquity",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Liabilities",
        "totalLabel": "Total liabilities"
       }
      }
     },
     "localname": "Liabilities",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LiabilitiesAndStockholdersEquity": {
     "auth_ref": [
      "r23",
      "r102",
      "r203",
      "r419",
      "r441",
      "r485",
      "r503"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of liabilities and equity items, including the portion of equity attributable to noncontrolling interests, if any.",
        "label": "Liabilities and Equity",
        "totalLabel": "Total liabilities and stockholders' equity"
       }
      }
     },
     "localname": "LiabilitiesAndStockholdersEquity",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LiabilitiesAndStockholdersEquityAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Liabilities and Equity [Abstract]",
        "terseLabel": "LIABILITIES AND STOCKHOLDERS' EQUITY"
       }
      }
     },
     "localname": "LiabilitiesAndStockholdersEquityAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LiabilitiesCurrent": {
     "auth_ref": [
      "r34",
      "r102",
      "r203",
      "r238",
      "r239",
      "r240",
      "r242",
      "r243",
      "r244",
      "r245",
      "r246",
      "r247",
      "r248",
      "r388",
      "r392",
      "r393",
      "r419",
      "r439",
      "r440",
      "r441"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 1.0,
       "parentTag": "us-gaap_Liabilities",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Liabilities, Current",
        "totalLabel": "Total current liabilities"
       }
      }
     },
     "localname": "LiabilitiesCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_LiabilitiesCurrentAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Liabilities, Current [Abstract]",
        "terseLabel": "Current liabilities:"
       }
      }
     },
     "localname": "LiabilitiesCurrentAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Long-term Debt, by Type, Current and Noncurrent [Abstract]",
        "terseLabel": "Convertible Debt [Abstract]"
       }
      }
     },
     "localname": "LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesConvertibleDebtDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_LongTermLoansFromBank": {
     "auth_ref": [
      "r15",
      "r484",
      "r500"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 6.0,
       "parentTag": "us-gaap_Liabilities",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Long-term mortgage debt"
       }
      }
     },
     "localname": "LongTermLoansFromBank",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NetCashProvidedByUsedInFinancingActivities": {
     "auth_ref": [
      "r83"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 5.0,
       "parentTag": "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Net Cash Provided by (Used in) Financing Activities",
        "totalLabel": "Net cash used in financing activities"
       }
      }
     },
     "localname": "NetCashProvidedByUsedInFinancingActivities",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Net Cash Provided by (Used in) Financing Activities [Abstract]",
        "terseLabel": "Financing activities:"
       }
      }
     },
     "localname": "NetCashProvidedByUsedInFinancingActivitiesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NetCashProvidedByUsedInInvestingActivities": {
     "auth_ref": [
      "r83"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 3.0,
       "parentTag": "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Net Cash Provided by (Used in) Investing Activities",
        "totalLabel": "Net cash (used in) provided by investing activities"
       }
      }
     },
     "localname": "NetCashProvidedByUsedInInvestingActivities",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Net Cash Provided by (Used in) Investing Activities [Abstract]",
        "terseLabel": "Investing activities:"
       }
      }
     },
     "localname": "NetCashProvidedByUsedInInvestingActivitiesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NetCashProvidedByUsedInOperatingActivities": {
     "auth_ref": [
      "r83",
      "r86",
      "r90"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 2.0,
       "parentTag": "us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect",
       "weight": 1.0
      }
     },
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Net Cash Provided by (Used in) Operating Activities",
        "totalLabel": "Net cash used in operating activities"
       }
      }
     },
     "localname": "NetCashProvidedByUsedInOperatingActivities",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Net Cash Provided by (Used in) Operating Activities [Abstract]",
        "terseLabel": "Operating activities:"
       }
      }
     },
     "localname": "NetCashProvidedByUsedInOperatingActivitiesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NetIncomeLoss": {
     "auth_ref": [
      "r2",
      "r52",
      "r54",
      "r60",
      "r63",
      "r90",
      "r102",
      "r112",
      "r114",
      "r115",
      "r116",
      "r117",
      "r120",
      "r121",
      "r126",
      "r153",
      "r161",
      "r164",
      "r167",
      "r169",
      "r203",
      "r238",
      "r239",
      "r240",
      "r242",
      "r243",
      "r244",
      "r245",
      "r246",
      "r247",
      "r248",
      "r406",
      "r419",
      "r488",
      "r505"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 0.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      },
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss": {
       "order": 0.0,
       "parentTag": "us-gaap_ComprehensiveIncomeNetOfTax",
       "weight": 1.0
      },
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": null,
       "parentTag": null,
       "root": true,
       "weight": null
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.",
        "label": "Net Income (Loss) Attributable to Parent",
        "terseLabel": "Net loss",
        "totalLabel": "Net loss"
       }
      }
     },
     "localname": "NetIncomeLoss",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "New Accounting Pronouncements, Policy [Policy Text Block]",
        "terseLabel": "Impact of Recently Issued Accounting Standards"
       }
      }
     },
     "localname": "NewAccountingPronouncementsPolicyPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_NonoperatingIncomeExpenseAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Nonoperating Income (Expense) [Abstract]",
        "terseLabel": "Other income (expense):"
       }
      }
     },
     "localname": "NonoperatingIncomeExpenseAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_NotesPayableFairValueDisclosure": {
     "auth_ref": [
      "r31"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Fair value portion of notes payable.",
        "label": "Notes Payable, Fair Value Disclosure",
        "terseLabel": "Fair value of convertible notes"
       }
      }
     },
     "localname": "NotesPayableFairValueDisclosure",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_NumberOfOperatingSegments": {
     "auth_ref": [
      "r148"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Number of operating segments"
       }
      }
     },
     "localname": "NumberOfOperatingSegments",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesSegmentInformationDetails"
     ],
     "xbrltype": "integerItemType"
    },
    "us-gaap_OperatingIncomeLoss": {
     "auth_ref": [
      "r153",
      "r161",
      "r164",
      "r167",
      "r169"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 1.0,
       "parentTag": "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The net result for the period of deducting operating expenses from operating revenues.",
        "label": "Operating Income (Loss)",
        "totalLabel": "Loss from operations"
       }
      }
     },
     "localname": "OperatingIncomeLoss",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense": {
     "auth_ref": [
      "r89"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 2.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of amortization expense for right-of-use asset from operating lease.",
        "label": "Operating Lease, Right-of-Use Asset, Amortization Expense",
        "terseLabel": "Amortization of right-of-use operating lease assets"
       }
      }
     },
     "localname": "OperatingLeaseRightOfUseAssetAmortizationExpense",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Basis of Presentation [Abstract]"
       }
      }
     },
     "localname": "OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock": {
     "auth_ref": [
      "r3",
      "r395"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The entire disclosure for organization, consolidation and basis of presentation of financial statements disclosure.",
        "label": "Organization, Consolidation and Presentation of Financial Statements Disclosure [Text Block]",
        "terseLabel": "Basis of Presentation"
       }
      }
     },
     "localname": "OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/BasisOfPresentation"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_OtherAssetsCurrent": {
     "auth_ref": [
      "r44",
      "r441"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 5.0,
       "parentTag": "us-gaap_AssetsCurrent",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of current assets classified as other.",
        "label": "Other Assets, Current",
        "terseLabel": "Other current assets"
       }
      }
     },
     "localname": "OtherAssetsCurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherAssetsNoncurrent": {
     "auth_ref": [
      "r29"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 6.0,
       "parentTag": "us-gaap_Assets",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of noncurrent assets classified as other.",
        "label": "Other Assets, Noncurrent",
        "terseLabel": "Deposits and other assets"
       }
      }
     },
     "localname": "OtherAssetsNoncurrent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent": {
     "auth_ref": [
      "r385",
      "r386",
      "r390"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Change in unrealized losses, net of tax"
       }
      }
     },
     "localname": "OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax": {
     "auth_ref": [
      "r46",
      "r49",
      "r420",
      "r421",
      "r423"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss": {
       "order": 2.0,
       "parentTag": "us-gaap_ComprehensiveIncomeNetOfTax",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Currency translation adjustment",
        "terseLabel": "Foreign currency translation"
       }
      }
     },
     "localname": "OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax": {
     "auth_ref": [
      "r47",
      "r49"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss": {
       "order": 1.0,
       "parentTag": "us-gaap_ComprehensiveIncomeNetOfTax",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "OCI, Debt Securities, Available-for-Sale, Unrealized Holding Gain (Loss), before Adjustment, after Tax",
        "terseLabel": "Unrealized losses on debt securities, net of tax"
       }
      }
     },
     "localname": "OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfComprehensiveLoss"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_OtherDebtSecuritiesMember": {
     "auth_ref": [
      "r190",
      "r213",
      "r320",
      "r412"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Investments in debt securities classified as other.",
        "label": "Other Debt Obligations [Member]",
        "terseLabel": "Other Municipal Debt Securities [Member]"
       }
      }
     },
     "localname": "OtherDebtSecuritiesMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_OtherNonoperatingIncomeExpense": {
     "auth_ref": [
      "r73"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 10.0,
       "parentTag": "us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of income (expense) related to nonoperating activities, classified as other.",
        "label": "Other Nonoperating Income (Expense)",
        "terseLabel": "Other income"
       }
      }
     },
     "localname": "OtherNonoperatingIncomeExpense",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PaymentsForHedgeFinancingActivities": {
     "auth_ref": [
      "r81",
      "r87"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Payments for Hedge, Financing Activities",
        "terseLabel": "Purchase of note hedges"
       }
      }
     },
     "localname": "PaymentsForHedgeFinancingActivities",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation": {
     "auth_ref": [
      "r79"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 11.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInFinancingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of cash outflow to satisfy grantee's tax withholding obligation for award under share-based payment arrangement.",
        "label": "Payment, Tax Withholding, Share-based Payment Arrangement",
        "negatedLabel": "Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options"
       }
      }
     },
     "localname": "PaymentsRelatedToTaxWithholdingForShareBasedCompensation",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt": {
     "auth_ref": [
      "r74",
      "r76",
      "r181"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 1.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInInvestingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Payments to Acquire Debt Securities, Available-for-sale",
        "negatedLabel": "Purchases of short-term investments"
       }
      }
     },
     "localname": "PaymentsToAcquireAvailableForSaleSecuritiesDebt",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PaymentsToAcquireIntangibleAssets": {
     "auth_ref": [
      "r77"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 5.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInInvestingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The cash outflow to acquire asset without physical form usually arising from contractual or other legal rights, excluding goodwill.",
        "label": "Payments to Acquire Intangible Assets",
        "negatedTerseLabel": "Acquisition of licenses and other assets, net"
       }
      }
     },
     "localname": "PaymentsToAcquireIntangibleAssets",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PaymentsToAcquirePropertyPlantAndEquipment": {
     "auth_ref": [
      "r77"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 3.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInInvestingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Payments to Acquire Property, Plant, and Equipment",
        "negatedLabel": "Purchases of property, plant and equipment"
       }
      }
     },
     "localname": "PaymentsToAcquirePropertyPlantAndEquipment",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PerformanceSharesMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Share-based payment arrangement awarded for meeting performance target.",
        "label": "Performance Shares [Member]",
        "terseLabel": "PRSUs [Member]"
       }
      }
     },
     "localname": "PerformanceSharesMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions": {
     "auth_ref": [
      "r78",
      "r351"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 3.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInFinancingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of cash inflow from issuance of shares under share-based payment arrangement. Includes, but is not limited to, option exercised.",
        "label": "Proceeds, Issuance of Shares, Share-based Payment Arrangement, Including Option Exercised",
        "terseLabel": "Proceeds from equity, net"
       }
      }
     },
     "localname": "ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ProceedsFromIssuanceOfWarrants": {
     "auth_ref": [
      "r78"
     ],
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The cash inflow from issuance of rights to purchase common shares at predetermined price (usually issued together with corporate debt).",
        "label": "Proceeds from Issuance of Warrants",
        "terseLabel": "Proceeds from issuance of warrants"
       }
      }
     },
     "localname": "ProceedsFromIssuanceOfWarrants",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities": {
     "auth_ref": [
      "r74",
      "r75",
      "r181"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 2.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInInvestingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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).",
        "label": "Proceeds from Sale and Maturity of Debt Securities, Available-for-sale",
        "terseLabel": "Proceeds from sale of short-term investments"
       }
      }
     },
     "localname": "ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ProductMember": {
     "auth_ref": [
      "r310"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Article or substance produced by nature, labor or machinery.",
        "label": "Product [Member]",
        "terseLabel": "TEGSEDI and WAYLIVRA Revenue, Net [Member]"
       }
      }
     },
     "localname": "ProductMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_PropertyPlantAndEquipmentByTypeAxis": {
     "auth_ref": [
      "r28",
      "r233"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by type of long-lived, physical assets used to produce goods and services and not intended for resale.",
        "label": "Long-Lived Tangible Asset [Axis]"
       }
      }
     },
     "localname": "PropertyPlantAndEquipmentByTypeAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_PropertyPlantAndEquipmentNet": {
     "auth_ref": [
      "r10",
      "r11",
      "r233",
      "r441",
      "r494",
      "r504"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 2.0,
       "parentTag": "us-gaap_Assets",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Property, Plant and Equipment, Net",
        "terseLabel": "Property, plant and equipment, net"
       }
      }
     },
     "localname": "PropertyPlantAndEquipmentNet",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_PropertyPlantAndEquipmentTypeDomain": {
     "auth_ref": [
      "r10",
      "r232"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Listing of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale. Examples include land, buildings, machinery and equipment, and other types of furniture and equipment including, but not limited to, office equipment, furniture and fixtures, and computer equipment and software.",
        "label": "Long-Lived Tangible Asset [Domain]"
       }
      }
     },
     "localname": "PropertyPlantAndEquipmentTypeDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesLeasesDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_PublicUtilitiesInventoryAxis": {
     "auth_ref": [
      "r24"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by type of inventory held.",
        "label": "Inventory [Axis]"
       }
      }
     },
     "localname": "PublicUtilitiesInventoryAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_PublicUtilitiesInventoryTypeDomain": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tangible personal property that is held for sale in the ordinary course of business, in process of production for such sale or is to be currently consumed in the production of goods or services to be available for sale.",
        "label": "Inventory [Domain]"
       }
      }
     },
     "localname": "PublicUtilitiesInventoryTypeDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesInventoryValuationDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_RealizedInvestmentGainsLosses": {
     "auth_ref": [
      "r511"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 12.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": -1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of realized gain (loss) on investment.",
        "label": "Realized Investment Gains (Losses)",
        "negatedLabel": "Gain on investments"
       }
      }
     },
     "localname": "RealizedInvestmentGainsLosses",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ReceivablesPolicyTextBlock": {
     "auth_ref": [
      "r174",
      "r176",
      "r177",
      "r178"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for receivable. Includes, but is not limited to, accounts receivable and financing receivable.",
        "label": "Receivable [Policy Text Block]",
        "terseLabel": "Contracts Receivable"
       }
      }
     },
     "localname": "ReceivablesPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_RepaymentsOfConvertibleDebt": {
     "auth_ref": [
      "r80"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Repayments of Convertible Debt",
        "terseLabel": "Repurchase of convertible notes"
       }
      }
     },
     "localname": "RepaymentsOfConvertibleDebt",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/ConvertibleDebtDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ResearchAndDevelopmentExpensePolicy": {
     "auth_ref": [
      "r360"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Research and Development Expense, Policy [Policy Text Block]",
        "terseLabel": "Research and Development Expenses"
       }
      }
     },
     "localname": "ResearchAndDevelopmentExpensePolicy",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_RestrictedStockUnitsRSUMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Share instrument which is convertible to stock or an equivalent amount of cash, after a specified period of time or when specified performance conditions are met.",
        "label": "Restricted Stock Units (RSUs) [Member]",
        "terseLabel": "RSUs [Member]"
       }
      }
     },
     "localname": "RestrictedStockUnitsRSUMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_RetainedEarningsAccumulatedDeficit": {
     "auth_ref": [
      "r19",
      "r294",
      "r355",
      "r441",
      "r502",
      "r520",
      "r522"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 4.0,
       "parentTag": "us-gaap_StockholdersEquity",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The cumulative amount of the reporting entity's undistributed earnings or deficit.",
        "label": "Retained Earnings (Accumulated Deficit)",
        "terseLabel": "Accumulated deficit"
       }
      }
     },
     "localname": "RetainedEarningsAccumulatedDeficit",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_RetainedEarningsMember": {
     "auth_ref": [
      "r0",
      "r109",
      "r110",
      "r111",
      "r113",
      "r119",
      "r121",
      "r206",
      "r352",
      "r353",
      "r354",
      "r370",
      "r371",
      "r404",
      "r517",
      "r519"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The cumulative amount of the reporting entity's undistributed earnings or deficit.",
        "label": "Retained Earnings [Member]",
        "terseLabel": "Accumulated Deficit [Member]"
       }
      }
     },
     "localname": "RetainedEarningsMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_RevenueFromContractWithCustomerAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Revenue from Contract with Customer [Abstract]",
        "terseLabel": "Revenue Recognition [Abstract]"
       }
      }
     },
     "localname": "RevenueFromContractWithCustomerAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax": {
     "auth_ref": [
      "r149",
      "r150",
      "r160",
      "r165",
      "r166",
      "r170",
      "r171",
      "r172",
      "r306",
      "r307",
      "r478"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 2.0,
       "parentTag": "us-gaap_OperatingIncomeLoss",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Revenue from Contract with Customer, Excluding Assessed Tax",
        "terseLabel": "Revenue"
       }
      }
     },
     "localname": "RevenueFromContractWithCustomerExcludingAssessedTax",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_RevenueFromContractWithCustomerMember": {
     "auth_ref": [
      "r142",
      "r172"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Revenue from satisfaction of performance obligation by transferring promised product and service to customer, when it serves as benchmark in concentration of risk calculation.",
        "label": "Revenue from Contract with Customer Benchmark [Member]",
        "verboseLabel": "Revenue [Member]"
       }
      }
     },
     "localname": "RevenueFromContractWithCustomerMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_RevenueFromContractWithCustomerPolicyTextBlock": {
     "auth_ref": [
      "r98",
      "r298",
      "r299",
      "r300",
      "r301",
      "r302",
      "r303",
      "r304",
      "r305",
      "r317"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for revenue from contract with customer.",
        "label": "Revenue from Contract with Customer [Policy Text Block]",
        "terseLabel": "Revenue Recognition"
       }
      }
     },
     "localname": "RevenueFromContractWithCustomerPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_RevenueRecognitionPolicyTextBlock": {
     "auth_ref": [
      "r98",
      "r99"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for revenue. Includes revenue from contract with customer and from other sources.",
        "label": "Revenue [Policy Text Block]",
        "terseLabel": "Deferred Revenue"
       }
      }
     },
     "localname": "RevenueRecognitionPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_RevenuesAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Revenues [Abstract]",
        "terseLabel": "Revenue:"
       }
      }
     },
     "localname": "RevenuesAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable": {
     "auth_ref": [
      "r381"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of information about collaborative arrangement and arrangement other than collaborative applicable to revenue-generating activity or operations.",
        "label": "Schedule of Collaborative Arrangements and Non-collaborative Arrangement Transactions [Table]"
       }
      }
     },
     "localname": "ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTable": {
     "auth_ref": [
      "r124",
      "r125",
      "r127",
      "r129",
      "r133"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The table contains disclosure pertaining to an entity's basic earnings per share.",
        "label": "Schedule of Earnings Per Share, Basic, by Common Class, Including Two Class Method [Table]"
       }
      }
     },
     "localname": "ScheduleOfEarningsPerShareBasicByCommonClassTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesBasicAndDilutedNetLossPerShareDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable": {
     "auth_ref": [
      "r334",
      "r347",
      "r357"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of information about amount recognized for award under share-based payment arrangement. Includes, but is not limited to, amount expensed in statement of income or comprehensive income, amount capitalized in statement of financial position, and corresponding reporting line item in financial statements.",
        "label": "Schedule of Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Table]"
       }
      }
     },
     "localname": "ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock": {
     "auth_ref": [
      "r334",
      "r347",
      "r357"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of allocation of amount expensed and capitalized for award under share-based payment arrangement to statement of income or comprehensive income and statement of financial position. Includes, but is not limited to, corresponding line item in financial statement.",
        "label": "Share-based Payment Arrangement, Expensed and Capitalized, Amount [Table Text Block]",
        "terseLabel": "Stock-Based Compensation Expense"
       }
      }
     },
     "localname": "ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable": {
     "auth_ref": [
      "r172"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure about the extent of the entity's reliance on its major customers.",
        "label": "Schedule of Revenue by Major Customers, by Reporting Segments [Table]"
       }
      }
     },
     "localname": "ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesContractsReceivableDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfInventoryCurrentTableTextBlock": {
     "auth_ref": [
      "r8",
      "r24",
      "r25",
      "r26"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of the carrying amount as of the balance sheet date of merchandise, goods, commodities, or supplies held for future sale or to be used in manufacturing, servicing or production process.",
        "label": "Schedule of Inventory, Current [Table Text Block]",
        "terseLabel": "Inventory"
       }
      }
     },
     "localname": "ScheduleOfInventoryCurrentTableTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable": {
     "auth_ref": [
      "r335",
      "r350"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of information about share-based payment arrangement.",
        "label": "Schedule of Share-based Compensation Arrangements by Share-based Payment Award [Table]"
       }
      }
     },
     "localname": "ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock": {
     "auth_ref": [
      "r341"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of the significant assumptions used during the year to estimate the fair value of employee stock purchase plans, including, but not limited to: (a) expected term, (b) expected volatility of the entity's shares, (c) expected dividends, (d) risk-free rate(s), and (e) discount for post-vesting restrictions.",
        "label": "Schedule of Share-based Payment Award, Employee Stock Purchase Plan, Valuation Assumptions [Table Text Block]",
        "terseLabel": "Weighted-Average Assumptions for ESPP"
       }
      }
     },
     "localname": "ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock": {
     "auth_ref": [
      "r341"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of the significant assumptions used during the year to estimate the fair value of stock options, including, but not limited to: (a) expected term of share options and similar instruments, (b) expected volatility of the entity's shares, (c) expected dividends, (d) risk-free rate(s), and (e) discount for post-vesting restrictions.",
        "label": "Schedule of Share-based Payment Award, Stock Options, Valuation Assumptions [Table Text Block]",
        "terseLabel": "Weighted-Average Assumptions for Stock Options"
       }
      }
     },
     "localname": "ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock": {
     "auth_ref": [
      "r193"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of investments in an unrealized loss position for which other-than-temporary impairments have not been recognized in earnings (including investments for which a portion of an other-than-temporary impairment has been recognized in other comprehensive income), including: (a) the aggregate related fair value of investments with unrealized losses, (b) the aggregate amount of unrealized losses (that is, the amount by which amortized cost basis exceeds fair value).",
        "label": "Schedule of Temporary Impairment Losses, Investments [Table Text Block]",
        "terseLabel": "Temporarily Impaired Investments"
       }
      }
     },
     "localname": "ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Debt and Equity Securities, FV-NI [Line Items]"
       }
      }
     },
     "localname": "ScheduleOfTradingSecuritiesAndOtherTradingAssetsLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of information about investment in debt security measured at fair value with change in fair value recognized in net income (trading) and investment in equity security with change in fair value recognized in net income (FV-NI).",
        "label": "Debt Securities, Trading, and Equity Securities, FV-NI [Table]"
       }
      }
     },
     "localname": "ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock": {
     "auth_ref": [
      "r140",
      "r142",
      "r143",
      "r144",
      "r416",
      "r418"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of the nature of a concentration, a benchmark to which it is compared, and the percentage that the risk is to the benchmark.",
        "label": "Schedules of Concentration of Risk, by Risk Factor [Table Text Block]",
        "verboseLabel": "Revenue from Collaborative Relationship with Biogen"
       }
      }
     },
     "localname": "SchedulesOfConcentrationOfRiskByRiskFactorTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Segment Reporting, Disclosure of Entity's Reportable Segments [Abstract]",
        "terseLabel": "Segment Information [Abstract]"
       }
      }
     },
     "localname": "SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesSegmentInformationDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_SegmentReportingPolicyPolicyTextBlock": {
     "auth_ref": [
      "r154",
      "r155",
      "r156",
      "r157",
      "r158",
      "r159",
      "r171"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for segment reporting.",
        "label": "Segment Reporting, Policy [Policy Text Block]",
        "terseLabel": "Segment Information"
       }
      }
     },
     "localname": "SegmentReportingPolicyPolicyTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_SellingGeneralAndAdministrativeExpense": {
     "auth_ref": [
      "r69"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations": {
       "order": 3.0,
       "parentTag": "us-gaap_CostsAndExpenses",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Selling, General and Administrative Expense",
        "terseLabel": "Selling, general and administrative"
       }
      }
     },
     "localname": "SellingGeneralAndAdministrativeExpense",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_SellingGeneralAndAdministrativeExpensesMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Primary financial statement caption encompassing selling, general and administrative expense.",
        "label": "Selling, General and Administrative Expenses [Member]",
        "verboseLabel": "Selling, General and Administrative Expense [Member]"
       }
      }
     },
     "localname": "SellingGeneralAndAdministrativeExpensesMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ShareBasedCompensation": {
     "auth_ref": [
      "r88"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows": {
       "order": 8.0,
       "parentTag": "us-gaap_NetCashProvidedByUsedInOperatingActivities",
       "weight": 1.0
      }
     },
     "crdr": "debit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Amount of noncash expense for share-based payment arrangement.",
        "label": "Share-based Payment Arrangement, Noncash Expense",
        "terseLabel": "Stock-based compensation expense"
       }
      }
     },
     "localname": "ShareBasedCompensation",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_ShareBasedCompensationAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Share-based Payment Arrangement, Noncash Expense [Abstract]",
        "terseLabel": "Stock-based Compensation Expense [Abstract]"
       }
      }
     },
     "localname": "ShareBasedCompensationAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Additional General Disclosures [Abstract]",
        "terseLabel": "RSUs and PRSUs [Abstract]"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1": {
     "auth_ref": [
      "r336"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Period",
        "terseLabel": "Vesting period"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions and Methodology [Abstract]",
        "terseLabel": "Weighted-Average Assumptions [Abstract]"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate": {
     "auth_ref": [
      "r344"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Dividend Rate",
        "terseLabel": "Dividend yield"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate": {
     "auth_ref": [
      "r345"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The risk-free interest rate assumption that is used in valuing an option on its own shares.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Risk Free Interest Rate",
        "terseLabel": "Risk-free interest rate"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate": {
     "auth_ref": [
      "r343"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Rate of weighted-average expected volatility for award under share-based payment arrangement.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Weighted Average Volatility Rate",
        "terseLabel": "Volatility"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award [Line Items]"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue": {
     "auth_ref": [
      "r340"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The weighted average grant-date fair value of options granted during the reporting period as calculated by applying the disclosed option pricing methodology.",
        "label": "Weighted-average grant date fair value (in dollars per share)"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "perShareItemType"
    },
    "us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain": {
     "auth_ref": [
      "r333",
      "r338"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Award under share-based payment arrangement.",
        "label": "Equity Award [Domain]"
       }
      }
     },
     "localname": "ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ShareBasedCompensationAwardTrancheOneMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "First portion of award under share-based payment arrangement differentiated by vesting feature, including, but not limited to, performance measure or service period.",
        "label": "Share-based Payment Arrangement, Tranche One [Member]",
        "terseLabel": "One-Year Period [Member]"
       }
      }
     },
     "localname": "ShareBasedCompensationAwardTrancheOneMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ShareBasedCompensationAwardTrancheThreeMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Third portion of award under share-based payment arrangement differentiated by vesting feature, including, but not limited to, performance measure or service period.",
        "label": "Three-Year Period [Member]"
       }
      }
     },
     "localname": "ShareBasedCompensationAwardTrancheThreeMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ShareBasedCompensationAwardTrancheTwoMember": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Second portion of award under share-based payment arrangement differentiated by vesting feature, including, but not limited to, performance measure or service period.",
        "label": "Two-Year Period [Member]"
       }
      }
     },
     "localname": "ShareBasedCompensationAwardTrancheTwoMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy": {
     "auth_ref": [
      "r335",
      "r339"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for award under share-based payment arrangement. Includes, but is not limited to, methodology and assumption used in measuring cost.",
        "label": "Share-based Payment Arrangement [Policy Text Block]",
        "terseLabel": "Stock-Based Compensation Expense"
       }
      }
     },
     "localname": "ShareBasedCompensationOptionAndIncentivePlansPolicy",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_ShareBasedPaymentArrangementEmployeeMember": {
     "auth_ref": [
      "r332",
      "r346"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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, but is not limited to, 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.",
        "label": "Share-based Payment Arrangement, Employee [Member]",
        "terseLabel": "Employees [Member]"
       }
      }
     },
     "localname": "ShareBasedPaymentArrangementEmployeeMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage": {
     "auth_ref": [
      "r336"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Percentage of vesting of award under share-based payment arrangement.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Rights, Percentage",
        "terseLabel": "Vesting percentage"
       }
      }
     },
     "localname": "SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "percentItemType"
    },
    "us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod": {
     "auth_ref": [
      "r337"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Expiration Period",
        "terseLabel": "Award term"
       }
      }
     },
     "localname": "SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1": {
     "auth_ref": [
      "r342",
      "r356"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Share-based Compensation Arrangement by Share-based Payment Award, Fair Value Assumptions, Expected Term",
        "terseLabel": "Expected life"
       }
      }
     },
     "localname": "SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "durationItemType"
    },
    "us-gaap_SharesIssued": {
     "auth_ref": [
      "r289"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Shares, Issued",
        "periodEndLabel": "Balance (in shares)",
        "periodStartLabel": "Balance (in shares)"
       }
      }
     },
     "localname": "SharesIssued",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Number of shares used to settle grantee's tax withholding obligation for award under share-based payment arrangement.",
        "label": "Share-based Payment Arrangement, Shares Withheld for Tax Withholding Obligation",
        "negatedLabel": "Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)"
       }
      }
     },
     "localname": "SharesPaidForTaxWithholdingForShareBasedCompensation",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_SignificantAccountingPoliciesTextBlock": {
     "auth_ref": [
      "r94",
      "r108"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "The entire disclosure for all significant accounting policies of the reporting entity.",
        "label": "Significant Accounting Policies [Text Block]",
        "terseLabel": "Significant Accounting Policies"
       }
      }
     },
     "localname": "SignificantAccountingPoliciesTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_StatementEquityComponentsAxis": {
     "auth_ref": [
      "r0",
      "r38",
      "r58",
      "r59",
      "r60",
      "r109",
      "r110",
      "r111",
      "r113",
      "r119",
      "r121",
      "r135",
      "r206",
      "r289",
      "r294",
      "r352",
      "r353",
      "r354",
      "r370",
      "r371",
      "r404",
      "r424",
      "r425",
      "r426",
      "r427",
      "r428",
      "r429",
      "r517",
      "r518",
      "r519",
      "r552"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by component of equity.",
        "label": "Equity Components [Axis]"
       }
      }
     },
     "localname": "StatementEquityComponentsAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementLineItems": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Statement [Line Items]"
       }
      }
     },
     "localname": "StatementLineItems",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementOfCashFlowsAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "CONSOLIDATED STATEMENTS OF CASH FLOWS [Abstract]"
       }
      }
     },
     "localname": "StatementOfCashFlowsAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementOfFinancialPositionAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "CONSOLIDATED BALANCE SHEETS [Abstract]"
       }
      }
     },
     "localname": "StatementOfFinancialPositionAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) [Abstract]"
       }
      }
     },
     "localname": "StatementOfIncomeAndComprehensiveIncomeAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementOfStockholdersEquityAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY [Abstract]"
       }
      }
     },
     "localname": "StatementOfStockholdersEquityAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "xbrltype": "stringItemType"
    },
    "us-gaap_StatementTable": {
     "auth_ref": [
      "r109",
      "r110",
      "r111",
      "r135",
      "r478"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Schedule reflecting a Statement of Income, Statement of Cash Flows, Statement of Financial Position, Statement of Shareholders' Equity and Other Comprehensive Income, or other statement as needed.",
        "label": "Statement [Table]"
       }
      }
     },
     "localname": "StatementTable",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations",
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation": {
     "auth_ref": [
      "r16",
      "r17",
      "r289",
      "r294"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Number, after forfeiture, of shares or units issued under share-based payment arrangement. Excludes shares or units issued under employee stock ownership plan (ESOP).",
        "label": "Shares Issued, Shares, Share-based Payment Arrangement, after Forfeiture",
        "verboseLabel": "Issuance of common stock in connection with employee stock plans (in shares)"
       }
      }
     },
     "localname": "StockIssuedDuringPeriodSharesShareBasedCompensation",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross": {
     "auth_ref": [],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Value, before forfeiture, of shares issued under share-based payment arrangement. Excludes employee stock ownership plan (ESOP).",
        "label": "Shares Issued, Value, Share-based Payment Arrangement, before Forfeiture",
        "terseLabel": "Issuance of common stock in connection with employee stock plans"
       }
      }
     },
     "localname": "StockIssuedDuringPeriodValueShareBasedCompensationGross",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_StockholdersEquity": {
     "auth_ref": [
      "r17",
      "r21",
      "r22",
      "r102",
      "r175",
      "r203",
      "r419",
      "r441"
     ],
     "calculation": {
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets": {
       "order": 2.0,
       "parentTag": "us-gaap_LiabilitiesAndStockholdersEquity",
       "weight": 1.0
      }
     },
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Stockholders' Equity Attributable to Parent",
        "totalLabel": "Total stockholders' equity"
       }
      }
     },
     "localname": "StockholdersEquity",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_StockholdersEquityAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Stockholders' Equity Attributable to Parent [Abstract]",
        "terseLabel": "Stockholders' equity:"
       }
      }
     },
     "localname": "StockholdersEquityAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheets",
      "http://ionispharma.com/role/CondensedConsolidatedBalanceSheetsParenthetical"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest": {
     "auth_ref": [
      "r0",
      "r1",
      "r59",
      "r102",
      "r109",
      "r110",
      "r111",
      "r113",
      "r119",
      "r203",
      "r206",
      "r294",
      "r352",
      "r353",
      "r354",
      "r370",
      "r371",
      "r383",
      "r384",
      "r394",
      "r404",
      "r419",
      "r424",
      "r425",
      "r429",
      "r518",
      "r519",
      "r552"
     ],
     "crdr": "credit",
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Stockholders' Equity, Including Portion Attributable to Noncontrolling Interest",
        "periodEndLabel": "Balance",
        "periodStartLabel": "Balance"
       }
      }
     },
     "localname": "StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfStockholdersEquity"
     ],
     "xbrltype": "monetaryItemType"
    },
    "us-gaap_SupplementalCashFlowInformationAbstract": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "label": "Supplemental Cash Flow Information [Abstract]",
        "terseLabel": "Supplemental disclosures of cash flow information:"
       }
      }
     },
     "localname": "SupplementalCashFlowInformationAbstract",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfCashFlows"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy": {
     "auth_ref": [
      "r179"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for treatment of receivables that are billable but have not been billed as of the balance sheet date.",
        "label": "Trade and Other Accounts Receivable, Unbilled Receivables, Policy [Policy Text Block]",
        "terseLabel": "Unbilled SPINRAZA Royalties"
       }
      }
     },
     "localname": "TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain": {
     "auth_ref": [
      "r188",
      "r189",
      "r196",
      "r197",
      "r198",
      "r275",
      "r288",
      "r403",
      "r442",
      "r443",
      "r444",
      "r445",
      "r446",
      "r447",
      "r448",
      "r449",
      "r450",
      "r451",
      "r452",
      "r453",
      "r454",
      "r455",
      "r456",
      "r457",
      "r458",
      "r459",
      "r460",
      "r461",
      "r462",
      "r463",
      "r464",
      "r465",
      "r466",
      "r467",
      "r468",
      "r469",
      "r470",
      "r471",
      "r544",
      "r545",
      "r546",
      "r547",
      "r548",
      "r549",
      "r550"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Instrument or contract that imposes a contractual obligation to deliver cash or another financial instrument or to exchange other financial instruments on potentially unfavorable terms and conveys a contractual right to receive cash or another financial instrument or to exchange other financial instruments on potentially favorable terms.",
        "label": "Financial Instruments [Domain]"
       }
      }
     },
     "localname": "TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesCashCashEquivalentsAndInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_TypeOfArrangementAxis": {
     "auth_ref": [
      "r381"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by collaborative arrangement and arrangement other than collaborative applicable to revenue-generating activity or operations.",
        "label": "Type of Arrangement and Non-arrangement Transactions [Axis]",
        "verboseLabel": "Type of Arrangement and Non-arrangement Transactions [Axis]"
       }
      }
     },
     "localname": "TypeOfArrangementAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CollaborativeArrangementsAndLicensingAgreementsDetails",
      "http://ionispharma.com/role/SignificantAccountingPoliciesRevenueRecognitionDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_USGovernmentAgenciesDebtSecuritiesMember": {
     "auth_ref": [
      "r105",
      "r320",
      "r493"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Debentures, notes, and other debt securities issued by US government agencies, for example, but not limited to, Government National Mortgage Association (GNMA or Ginnie Mae). Excludes US treasury securities and debt issued by government-sponsored Enterprises (GSEs), for example, but is not limited to, Federal Home Loan Mortgage Corporation (FHLMC or Freddie Mac), Federal National Mortgage Association (FNMA or Fannie Mae), and the Federal Home Loan Bank (FHLB).",
        "label": "US Government Agencies Debt Securities [Member]",
        "terseLabel": "Debt Securities Issued by U.S. Government Agencies [Member]"
       }
      }
     },
     "localname": "USGovernmentAgenciesDebtSecuritiesMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_USStatesAndPoliticalSubdivisionsMember": {
     "auth_ref": [
      "r320",
      "r523"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Bonds or similar securities issued by state, city, or local US governments or the agencies operated by state, city, or local governments. Debt securities issued by state governments may include bond issuances of US state authorities including, for example, but not limited to, housing authorities, dormitory authorities, and general obligations while debt securities issued by political subdivisions of US states would include, for example, debt issuances by county, borough, city, or municipal governments.",
        "label": "US States and Political Subdivisions Debt Securities [Member]",
        "terseLabel": "Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]"
       }
      }
     },
     "localname": "USStatesAndPoliticalSubdivisionsMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_USTreasurySecuritiesMember": {
     "auth_ref": [
      "r105",
      "r320",
      "r327",
      "r493"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "This category includes information about debt securities issued by the United States Department of the Treasury and backed by the United States government. Such securities primarily consist of treasury bills (short-term maturities - one year or less), treasury notes (intermediate term maturities - two to ten years), and treasury bonds (long-term maturities - ten to thirty years).",
        "label": "US Treasury Securities [Member]",
        "terseLabel": "Debt Securities Issued by the U.S. Treasury [Member]"
       }
      }
     },
     "localname": "USTreasurySecuritiesMember",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/FairValueMeasurementsDetails",
      "http://ionispharma.com/role/InvestmentsInvestmentsTemporarilyImpairedDetails",
      "http://ionispharma.com/role/InvestmentsSummaryOfInvestmentsDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock": {
     "auth_ref": [],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Tabular disclosure of unrealized gains and losses on investments.",
        "label": "Unrealized Gain (Loss) on Investments [Table Text Block]",
        "terseLabel": "Summary of Investments"
       }
      }
     },
     "localname": "UnrealizedGainLossOnInvestmentsTableTextBlock",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/InvestmentsTables"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_UseOfEstimates": {
     "auth_ref": [
      "r136",
      "r137",
      "r138",
      "r139",
      "r145",
      "r146",
      "r147"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Disclosure of accounting policy for the use of estimates in the preparation of financial statements in conformity with generally accepted accounting principles.",
        "label": "Use of Estimates, Policy [Policy Text Block]",
        "terseLabel": "Use of Estimates"
       }
      }
     },
     "localname": "UseOfEstimates",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesPolicies"
     ],
     "xbrltype": "textBlockItemType"
    },
    "us-gaap_VestingAxis": {
     "auth_ref": [
      "r350"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Information by vesting schedule of award under share-based payment arrangement.",
        "label": "Vesting [Axis]"
       }
      }
     },
     "localname": "VestingAxis",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "stringItemType"
    },
    "us-gaap_VestingDomain": {
     "auth_ref": [
      "r350"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "Vesting schedule of award under share-based payment arrangement.",
        "label": "Vesting [Domain]"
       }
      }
     },
     "localname": "VestingDomain",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/SignificantAccountingPoliciesStockbasedCompensationExpenseDetails"
     ],
     "xbrltype": "domainItemType"
    },
    "us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding": {
     "auth_ref": [
      "r123",
      "r129"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Shares used in computing diluted net loss per share (in shares)"
       }
      }
     },
     "localname": "WeightedAverageNumberOfDilutedSharesOutstanding",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "sharesItemType"
    },
    "us-gaap_WeightedAverageNumberOfSharesOutstandingBasic": {
     "auth_ref": [
      "r122",
      "r129"
     ],
     "lang": {
      "en-us": {
       "role": {
        "documentation": "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.",
        "label": "Shares used in computing basic net loss per share (in shares)"
       }
      }
     },
     "localname": "WeightedAverageNumberOfSharesOutstandingBasic",
     "nsuri": "http://fasb.org/us-gaap/2021-01-31",
     "presentation": [
      "http://ionispharma.com/role/CondensedConsolidatedStatementsOfOperations"
     ],
     "xbrltype": "sharesItemType"
    }
   },
   "unitCount": 13
  }
 },
 "std_ref": {
  "r0": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "105",
   "URI": "http://asc.fasb.org/extlink&oid=124434974&loc=SL124442142-165695"
  },
  "r1": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "105",
   "URI": "http://asc.fasb.org/extlink&oid=124434974&loc=SL124442142-165695"
  },
  "r10": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(13))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r100": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.4-08(c))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690"
  },
  "r101": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.4-08(f))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690"
  },
  "r102": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.4-08(g)(1)(ii))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690"
  },
  "r103": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.4-08(h)(2))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690"
  },
  "r104": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.4-08(h))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690"
  },
  "r105": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.4-08(m)(1)(ii)(A))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690"
  },
  "r106": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.4-08(n))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690"
  },
  "r107": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.12-04(a))",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=120395691&loc=d3e24072-122690"
  },
  "r108": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "235",
   "URI": "http://asc.fasb.org/topic&trid=2122369"
  },
  "r109": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "23",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124436220&loc=d3e21914-107793"
  },
  "r11": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(14))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r110": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "24",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124436220&loc=d3e21930-107793"
  },
  "r111": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124436220&loc=d3e21711-107793"
  },
  "r112": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)(2)",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22499-107794"
  },
  "r113": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)(3)",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22499-107794"
  },
  "r114": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22694-107794"
  },
  "r115": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22694-107794"
  },
  "r116": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22583-107794"
  },
  "r117": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22595-107794"
  },
  "r118": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22644-107794"
  },
  "r119": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22644-107794"
  },
  "r12": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(19))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r120": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22658-107794"
  },
  "r121": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "9",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "250",
   "URI": "http://asc.fasb.org/extlink&oid=124431687&loc=d3e22663-107794"
  },
  "r122": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=125511455&loc=d3e1448-109256"
  },
  "r123": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "16",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=125511455&loc=d3e1505-109256"
  },
  "r124": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=125511455&loc=d3e1252-109256"
  },
  "r125": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=125511455&loc=d3e1278-109256"
  },
  "r126": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "60B",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=125511455&loc=SL5780133-109256"
  },
  "r127": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "60B",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=125511455&loc=SL5780133-109256"
  },
  "r128": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=125511455&loc=d3e1337-109256"
  },
  "r129": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=124432515&loc=d3e3550-109257"
  },
  "r13": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(2))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r130": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=124432515&loc=d3e3550-109257"
  },
  "r131": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=124432515&loc=d3e3630-109257"
  },
  "r132": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=125512782&loc=d3e3842-109258"
  },
  "r133": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "52",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Topic": "260",
   "URI": "http://asc.fasb.org/extlink&oid=125512782&loc=d3e4984-109258"
  },
  "r134": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "270",
   "URI": "http://asc.fasb.org/extlink&oid=124437754&loc=d3e543-108305"
  },
  "r135": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "272",
   "URI": "http://asc.fasb.org/extlink&oid=125520817&loc=d3e70191-108054"
  },
  "r136": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e5967-108592"
  },
  "r137": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e5967-108592"
  },
  "r138": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6161-108592"
  },
  "r139": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "12",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6191-108592"
  },
  "r14": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(20))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r140": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "16",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6327-108592"
  },
  "r141": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "18",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6351-108592"
  },
  "r142": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "18",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6351-108592"
  },
  "r143": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6404-108592"
  },
  "r144": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "21",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6442-108592"
  },
  "r145": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6061-108592"
  },
  "r146": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6132-108592"
  },
  "r147": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "9",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "275",
   "URI": "http://asc.fasb.org/extlink&oid=99393423&loc=d3e6143-108592"
  },
  "r148": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "18",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8672-108599"
  },
  "r149": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "22",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8736-108599"
  },
  "r15": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(22))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r150": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "22",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8736-108599"
  },
  "r151": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "22",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8736-108599"
  },
  "r152": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "22",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(h)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8736-108599"
  },
  "r153": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "22",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8736-108599"
  },
  "r154": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "29",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8864-108599"
  },
  "r155": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "29",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8864-108599"
  },
  "r156": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "29",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8864-108599"
  },
  "r157": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "29",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8864-108599"
  },
  "r158": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "29",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(e)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8864-108599"
  },
  "r159": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "29",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8864-108599"
  },
  "r16": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(28))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r160": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "30",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8906-108599"
  },
  "r161": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "30",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8906-108599"
  },
  "r162": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "30",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8906-108599"
  },
  "r163": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "30",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8906-108599"
  },
  "r164": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "31",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8924-108599"
  },
  "r165": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "32",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8933-108599"
  },
  "r166": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "32",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8933-108599"
  },
  "r167": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "32",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8933-108599"
  },
  "r168": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "32",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8933-108599"
  },
  "r169": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "32",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e8933-108599"
  },
  "r17": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(29))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r170": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "40",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e9031-108599"
  },
  "r171": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "41",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e9038-108599"
  },
  "r172": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "42",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "280",
   "URI": "http://asc.fasb.org/extlink&oid=123359005&loc=d3e9054-108599"
  },
  "r173": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "310",
   "URI": "http://asc.fasb.org/extlink&oid=124259787&loc=d3e4647-111522"
  },
  "r174": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "310",
   "URI": "http://asc.fasb.org/extlink&oid=123577603&loc=d3e5033-111524"
  },
  "r175": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SAB Topic 4.E)",
   "Topic": "310",
   "URI": "http://asc.fasb.org/extlink&oid=122038336&loc=d3e74512-122707"
  },
  "r176": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "310",
   "URI": "http://asc.fasb.org/extlink&oid=84159169&loc=d3e10133-111534"
  },
  "r177": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "310",
   "URI": "http://asc.fasb.org/extlink&oid=84159169&loc=d3e10149-111534"
  },
  "r178": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "310",
   "URI": "http://asc.fasb.org/extlink&oid=84159169&loc=d3e10178-111534"
  },
  "r179": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "310",
   "URI": "http://asc.fasb.org/topic&trid=2196771"
  },
  "r18": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(30)(a)(1))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r180": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=124260329&loc=d3e26610-111562"
  },
  "r181": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=124260329&loc=d3e26853-111562"
  },
  "r182": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=124260329&loc=d3e26626-111562"
  },
  "r183": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27405-111563"
  },
  "r184": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27161-111563"
  },
  "r185": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(aa)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27161-111563"
  },
  "r186": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27161-111563"
  },
  "r187": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27161-111563"
  },
  "r188": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27232-111563"
  },
  "r189": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=SL120269820-111563"
  },
  "r19": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(30)(a)(3))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r190": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27290-111563"
  },
  "r191": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)(1)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27290-111563"
  },
  "r192": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)(2)",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27290-111563"
  },
  "r193": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27290-111563"
  },
  "r194": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "320",
   "URI": "http://asc.fasb.org/extlink&oid=123581744&loc=d3e27337-111563"
  },
  "r195": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "320",
   "URI": "http://asc.fasb.org/topic&trid=2196928"
  },
  "r196": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "321",
   "URI": "http://asc.fasb.org/extlink&oid=123583765&loc=SL75117539-209714"
  },
  "r197": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "321",
   "URI": "http://asc.fasb.org/extlink&oid=123583765&loc=SL75117539-209714"
  },
  "r198": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "321",
   "URI": "http://asc.fasb.org/extlink&oid=123583765&loc=SL75117539-209714"
  },
  "r199": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "321",
   "URI": "http://asc.fasb.org/extlink&oid=123583765&loc=SL75117546-209714"
  },
  "r2": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "205",
   "URI": "http://asc.fasb.org/extlink&oid=109222650&loc=SL51721683-107760"
  },
  "r20": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(30)(a)(4))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r200": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "321",
   "URI": "http://asc.fasb.org/topic&trid=75115024"
  },
  "r201": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)(1)",
   "Topic": "323",
   "URI": "http://asc.fasb.org/extlink&oid=114001798&loc=d3e33918-111571"
  },
  "r202": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)(2)",
   "Topic": "323",
   "URI": "http://asc.fasb.org/extlink&oid=114001798&loc=d3e33918-111571"
  },
  "r203": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "323",
   "URI": "http://asc.fasb.org/extlink&oid=114001798&loc=d3e33918-111571"
  },
  "r204": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "323",
   "URI": "http://asc.fasb.org/topic&trid=2196965"
  },
  "r205": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "325",
   "URI": "http://asc.fasb.org/topic&trid=2197064"
  },
  "r206": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=122640432&loc=SL121648383-210437"
  },
  "r207": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124255953&loc=SL82919244-210447"
  },
  "r208": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124255953&loc=SL82919249-210447"
  },
  "r209": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "14",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124255953&loc=SL82919253-210447"
  },
  "r21": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(30))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r210": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "16",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124255953&loc=SL82919258-210447"
  },
  "r211": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124255953&loc=SL82919230-210447"
  },
  "r212": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124258926&loc=SL82898722-210454"
  },
  "r213": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(a)",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124269663&loc=SL82922888-210455"
  },
  "r214": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(a)(1)",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124269663&loc=SL82922888-210455"
  },
  "r215": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(a)(2)",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124269663&loc=SL82922888-210455"
  },
  "r216": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(b)(3)",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124269663&loc=SL82922888-210455"
  },
  "r217": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124269663&loc=SL82922888-210455"
  },
  "r218": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124269663&loc=SL82922890-210455"
  },
  "r219": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124269663&loc=SL82922895-210455"
  },
  "r22": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(31))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r220": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "9",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=124269663&loc=SL82922900-210455"
  },
  "r221": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "30",
   "Topic": "326",
   "URI": "http://asc.fasb.org/extlink&oid=121590138&loc=SL82922954-210456"
  },
  "r222": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "330",
   "URI": "http://asc.fasb.org/extlink&oid=116847112&loc=d3e4492-108314"
  },
  "r223": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "330",
   "URI": "http://asc.fasb.org/extlink&oid=116847112&loc=d3e4556-108314"
  },
  "r224": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "330",
   "URI": "http://asc.fasb.org/topic&trid=2126998"
  },
  "r225": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "350",
   "URI": "http://asc.fasb.org/extlink&oid=6388964&loc=d3e16225-109274"
  },
  "r226": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(a)",
   "Topic": "350",
   "URI": "http://asc.fasb.org/extlink&oid=66006027&loc=d3e16323-109275"
  },
  "r227": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(a)(1)",
   "Topic": "350",
   "URI": "http://asc.fasb.org/extlink&oid=66006027&loc=d3e16323-109275"
  },
  "r228": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(a)(2)",
   "Topic": "350",
   "URI": "http://asc.fasb.org/extlink&oid=66006027&loc=d3e16323-109275"
  },
  "r229": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(b)",
   "Topic": "350",
   "URI": "http://asc.fasb.org/extlink&oid=66006027&loc=d3e16373-109275"
  },
  "r23": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(32))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r230": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "360",
   "URI": "http://asc.fasb.org/extlink&oid=123351718&loc=d3e2443-110228"
  },
  "r231": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "360",
   "URI": "http://asc.fasb.org/extlink&oid=6391035&loc=d3e2868-110229"
  },
  "r232": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "360",
   "URI": "http://asc.fasb.org/extlink&oid=6391035&loc=d3e2868-110229"
  },
  "r233": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "360",
   "URI": "http://asc.fasb.org/extlink&oid=6391035&loc=d3e2868-110229"
  },
  "r234": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "360",
   "URI": "http://asc.fasb.org/extlink&oid=109226691&loc=d3e2941-110230"
  },
  "r235": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "360",
   "URI": "http://asc.fasb.org/extlink&oid=109226691&loc=d3e2941-110230"
  },
  "r236": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "420",
   "URI": "http://asc.fasb.org/extlink&oid=6394359&loc=d3e17939-110869"
  },
  "r237": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123465755&loc=d3e1835-112601"
  },
  "r238": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-01(a)(4)(i))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756"
  },
  "r239": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-01(a)(4)(ii))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756"
  },
  "r24": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(6)(a))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r240": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-01(a)(4)(iii)(A))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756"
  },
  "r241": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-01(a)(4)(iii))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756"
  },
  "r242": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-01(a)(4)(iv))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756"
  },
  "r243": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-01(a)(5))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442526-122756"
  },
  "r244": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-02(a)(4)(i))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756"
  },
  "r245": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-02(a)(4)(iii)(A))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756"
  },
  "r246": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-02(a)(4)(iii)(B))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756"
  },
  "r247": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-02(a)(4)(iv))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756"
  },
  "r248": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.13-02(a)(5))",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=124359900&loc=SL124442552-122756"
  },
  "r249": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r25": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(6)(b))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r250": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r251": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(c)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r252": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r253": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(e)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r254": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(f)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r255": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(g)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r256": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(h)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r257": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(i)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r258": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495323-112611"
  },
  "r259": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1C",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495334-112611"
  },
  "r26": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(6)(c))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r260": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1C",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495334-112611"
  },
  "r261": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1C",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(c)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495334-112611"
  },
  "r262": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1D",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495340-112611"
  },
  "r263": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1D",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495340-112611"
  },
  "r264": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1D",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(c)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495340-112611"
  },
  "r265": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1E",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495348-112611"
  },
  "r266": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1E",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495348-112611"
  },
  "r267": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1E",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(c)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495348-112611"
  },
  "r268": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1E",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495348-112611"
  },
  "r269": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1F",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495355-112611"
  },
  "r27": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.1)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r270": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1F",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495355-112611"
  },
  "r271": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1F",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)(1)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495355-112611"
  },
  "r272": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1F",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)(2)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495355-112611"
  },
  "r273": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1I",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611"
  },
  "r274": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1I",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611"
  },
  "r275": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1I",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(c)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611"
  },
  "r276": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1I",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466505&loc=SL123495371-112611"
  },
  "r277": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)(1)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466204&loc=SL6031897-161870"
  },
  "r278": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466204&loc=SL6031898-161870"
  },
  "r279": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466204&loc=SL6036836-161870"
  },
  "r28": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.14)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r280": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "69B",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466577&loc=SL123495735-112612"
  },
  "r281": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "69C",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466577&loc=SL123495737-112612"
  },
  "r282": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "69E",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466577&loc=SL123495743-112612"
  },
  "r283": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "69F",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123466577&loc=SL123495745-112612"
  },
  "r284": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "40",
   "SubTopic": "50",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123467658&loc=d3e12317-112629"
  },
  "r285": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "40",
   "SubTopic": "50",
   "Topic": "470",
   "URI": "http://asc.fasb.org/extlink&oid=123467658&loc=d3e12355-112629"
  },
  "r286": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "470",
   "URI": "http://asc.fasb.org/topic&trid=2208564"
  },
  "r287": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "505",
   "URI": "http://asc.fasb.org/extlink&oid=123467817&loc=SL123496158-112644"
  },
  "r288": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "18",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "505",
   "URI": "http://asc.fasb.org/extlink&oid=123467817&loc=SL123496189-112644"
  },
  "r289": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "505",
   "URI": "http://asc.fasb.org/extlink&oid=123467817&loc=d3e21463-112644"
  },
  "r29": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.17)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r290": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "505",
   "URI": "http://asc.fasb.org/extlink&oid=123467817&loc=d3e21475-112644"
  },
  "r291": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "505",
   "URI": "http://asc.fasb.org/extlink&oid=123467817&loc=d3e21506-112644"
  },
  "r292": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "505",
   "URI": "http://asc.fasb.org/extlink&oid=123467817&loc=d3e21521-112644"
  },
  "r293": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "505",
   "URI": "http://asc.fasb.org/extlink&oid=123467817&loc=d3e21538-112644"
  },
  "r294": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.3-04)",
   "Topic": "505",
   "URI": "http://asc.fasb.org/extlink&oid=120397183&loc=d3e187085-122770"
  },
  "r295": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123360276&loc=SL49130531-203044"
  },
  "r296": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123360276&loc=SL49130532-203044"
  },
  "r297": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123360276&loc=SL49130533-203044"
  },
  "r298": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "17",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130561-203045"
  },
  "r299": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "18",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130563-203045"
  },
  "r3": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "205",
   "URI": "http://asc.fasb.org/topic&trid=2122149"
  },
  "r30": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.19(a))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r300": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "18",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130563-203045"
  },
  "r301": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "19",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130564-203045"
  },
  "r302": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130566-203045"
  },
  "r303": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130566-203045"
  },
  "r304": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130566-203045"
  },
  "r305": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130566-203045"
  },
  "r306": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130543-203045"
  },
  "r307": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130545-203045"
  },
  "r308": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130549-203045"
  },
  "r309": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123351226&loc=SL49130549-203045"
  },
  "r31": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.19,20,22)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r310": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "91",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123410239&loc=SL49130690-203046-203046"
  },
  "r311": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "91",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123410239&loc=SL49130690-203046-203046"
  },
  "r312": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "91",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123410239&loc=SL49130690-203046-203046"
  },
  "r313": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "91",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123410239&loc=SL49130690-203046-203046"
  },
  "r314": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "91",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Subparagraph": "(e)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123410239&loc=SL49130690-203046-203046"
  },
  "r315": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "91",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Subparagraph": "(f)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123410239&loc=SL49130690-203046-203046"
  },
  "r316": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "91",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Subparagraph": "(g)",
   "Topic": "606",
   "URI": "http://asc.fasb.org/extlink&oid=123410239&loc=SL49130690-203046-203046"
  },
  "r317": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "606",
   "URI": "http://asc.fasb.org/topic&trid=49130388"
  },
  "r318": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "705",
   "URI": "http://asc.fasb.org/topic&trid=2122478"
  },
  "r319": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)(i)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920"
  },
  "r32": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.19-26)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r320": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)(ii)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920"
  },
  "r321": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)(iv)(01)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920"
  },
  "r322": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)(iv)(02)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920"
  },
  "r323": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)(iv)(02)(A)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920"
  },
  "r324": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)(iv)(02)(B)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920"
  },
  "r325": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)(iv)(02)(C)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920"
  },
  "r326": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(d)(iv)(03)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=123447040&loc=d3e1928-114920"
  },
  "r327": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "17",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=123450688&loc=d3e4179-114921"
  },
  "r328": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "80",
   "Subparagraph": "(d)",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=65877416&loc=SL14450657-114947"
  },
  "r329": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "80",
   "Topic": "715",
   "URI": "http://asc.fasb.org/extlink&oid=35742348&loc=SL14450788-114948"
  },
  "r33": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.20)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r330": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1D",
   "Publisher": "FASB",
   "Section": "35",
   "SubTopic": "10",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=123468992&loc=SL116886442-113899"
  },
  "r331": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "35",
   "SubTopic": "10",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=123468992&loc=d3e4534-113899"
  },
  "r332": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "35",
   "SubTopic": "10",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=123468992&loc=d3e4549-113899"
  },
  "r333": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5047-113901"
  },
  "r334": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5047-113901"
  },
  "r335": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5047-113901"
  },
  "r336": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)(1)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r337": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)(2)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r338": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a),(g)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r339": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b),(f)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r34": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.21)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r340": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)(1)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r341": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)(2)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r342": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)(2)(i)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r343": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)(2)(ii)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r344": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)(2)(iii)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r345": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)(2)(iv)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r346": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(g)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r347": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(h)(1)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r348": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(h)(1)(i)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r349": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(i)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r35": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.22(a)(1))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r350": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=d3e5070-113901"
  },
  "r351": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=120381028&loc=SL79508275-113901"
  },
  "r352": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(e)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=121322162&loc=SL121327923-165333"
  },
  "r353": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(f)(1)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=121322162&loc=SL121327923-165333"
  },
  "r354": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(f)(2)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=121322162&loc=SL121327923-165333"
  },
  "r355": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(g)(2)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=121322162&loc=SL121327923-165333"
  },
  "r356": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SAB Topic 14.D.2)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=122041274&loc=d3e301413-122809"
  },
  "r357": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SAB Topic 14.F)",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=122041274&loc=d3e301413-122809"
  },
  "r358": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "12",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=122142933&loc=d3e11149-113907"
  },
  "r359": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "20",
   "Topic": "718",
   "URI": "http://asc.fasb.org/extlink&oid=122142933&loc=d3e11178-113907"
  },
  "r36": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.22(a)(2))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r360": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "730",
   "URI": "http://asc.fasb.org/extlink&oid=6420194&loc=d3e21568-108373"
  },
  "r361": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=123427490&loc=d3e32247-109318"
  },
  "r362": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=123427490&loc=d3e32280-109318"
  },
  "r363": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=121826272&loc=d3e32672-109319"
  },
  "r364": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "14",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=121826272&loc=d3e32705-109319"
  },
  "r365": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "17",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=121826272&loc=d3e32809-109319"
  },
  "r366": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "19",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=121826272&loc=d3e32840-109319"
  },
  "r367": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=121826272&loc=d3e32847-109319"
  },
  "r368": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "21",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=121826272&loc=d3e32857-109319"
  },
  "r369": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "9",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=121826272&loc=d3e32639-109319"
  },
  "r37": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.22)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r370": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(d)(2)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=123459177&loc=SL121830611-158277"
  },
  "r371": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(d)(3)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=123459177&loc=SL121830611-158277"
  },
  "r372": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SAB TOPIC 6.I.5.Q1)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=122134291&loc=d3e330036-122817"
  },
  "r373": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SAB TOPIC 6.I.7)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=122134291&loc=d3e330036-122817"
  },
  "r374": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SAB Topic 11.C)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=122134291&loc=d3e330215-122817"
  },
  "r375": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=123586238&loc=d3e38679-109324"
  },
  "r376": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "270",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=6424409&loc=d3e44925-109338"
  },
  "r377": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(a)",
   "Topic": "740",
   "URI": "http://asc.fasb.org/extlink&oid=6424122&loc=d3e41874-109331"
  },
  "r378": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "740",
   "URI": "http://asc.fasb.org/topic&trid=2144680"
  },
  "r379": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "808",
   "URI": "http://asc.fasb.org/extlink&oid=6931272&loc=SL5834143-161434"
  },
  "r38": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.29-31)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r380": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "808",
   "URI": "http://asc.fasb.org/extlink&oid=6931272&loc=SL5834143-161434"
  },
  "r381": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "808",
   "URI": "http://asc.fasb.org/extlink&oid=6931272&loc=SL5834143-161434"
  },
  "r382": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "808",
   "URI": "http://asc.fasb.org/topic&trid=5833765"
  },
  "r383": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=123454820&loc=SL4568447-111683"
  },
  "r384": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "16",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=123454820&loc=SL4568740-111683"
  },
  "r385": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "19",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=123454820&loc=SL4569616-111683"
  },
  "r386": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=123454820&loc=SL4569643-111683"
  },
  "r387": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=116870748&loc=SL6758485-165988"
  },
  "r388": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=116870748&loc=SL6758485-165988"
  },
  "r389": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=109239629&loc=d3e5614-111684"
  },
  "r39": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.6(a)(1))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r390": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)(3)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=109239629&loc=SL4573702-111684"
  },
  "r391": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c),(3)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=109239629&loc=SL4573702-111684"
  },
  "r392": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(bb)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=123419778&loc=d3e5710-111685"
  },
  "r393": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=123419778&loc=d3e5710-111685"
  },
  "r394": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4I",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Topic": "810",
   "URI": "http://asc.fasb.org/extlink&oid=120409616&loc=SL4590271-111686"
  },
  "r395": {
   "Name": "Accounting Standards Codification",
   "Publisher": "FASB",
   "Topic": "810",
   "URI": "http://asc.fasb.org/topic&trid=2197479"
  },
  "r396": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=125515794&loc=SL5579240-113959"
  },
  "r397": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=125515794&loc=SL5579245-113959"
  },
  "r398": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=125515794&loc=d3e41620-113959"
  },
  "r399": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=125515794&loc=d3e41638-113959"
  },
  "r4": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=124098289&loc=d3e6676-107765"
  },
  "r40": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.6(a)(3))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r400": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=125515794&loc=SL5618551-113959"
  },
  "r401": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=125515794&loc=SL5624163-113959"
  },
  "r402": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=125515794&loc=d3e41675-113959"
  },
  "r403": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "40",
   "Subparagraph": "(f)",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=123477628&loc=d3e90205-114008"
  },
  "r404": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "40",
   "Subparagraph": "(e)(3)",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=123482062&loc=SL123482106-238011"
  },
  "r405": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "40",
   "Subparagraph": "(e)(4)",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=123482062&loc=SL123482106-238011"
  },
  "r406": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "40",
   "Subparagraph": "(f)",
   "Topic": "815",
   "URI": "http://asc.fasb.org/extlink&oid=123482062&loc=SL123482106-238011"
  },
  "r407": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=123874694&loc=d3e19207-110258"
  },
  "r408": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=123874694&loc=d3e19207-110258"
  },
  "r409": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(bb)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=123874694&loc=d3e19207-110258"
  },
  "r41": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.6(a)(4))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r410": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(bbb)(1)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=123874694&loc=d3e19207-110258"
  },
  "r411": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(bbb)(2)",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=123874694&loc=d3e19207-110258"
  },
  "r412": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=123874694&loc=d3e19207-110258"
  },
  "r413": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=123874694&loc=d3e19279-110258"
  },
  "r414": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "820",
   "URI": "http://asc.fasb.org/extlink&oid=123874694&loc=SL6742756-110258"
  },
  "r415": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "825",
   "URI": "http://asc.fasb.org/extlink&oid=123594786&loc=SL75136599-209740"
  },
  "r416": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "825",
   "URI": "http://asc.fasb.org/extlink&oid=123594938&loc=d3e13531-108611"
  },
  "r417": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "21",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "825",
   "URI": "http://asc.fasb.org/extlink&oid=123594938&loc=d3e13537-108611"
  },
  "r418": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "21",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "825",
   "URI": "http://asc.fasb.org/extlink&oid=123594938&loc=d3e13537-108611"
  },
  "r419": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)",
   "Topic": "825",
   "URI": "http://asc.fasb.org/extlink&oid=123596393&loc=d3e14064-108612"
  },
  "r42": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.6(a))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r420": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "9",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=120253306&loc=d3e28129-110885"
  },
  "r421": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "35",
   "SubTopic": "20",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=123602790&loc=d3e30304-110892"
  },
  "r422": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "230",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=123444420&loc=d3e33268-110906"
  },
  "r423": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "12",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=118261656&loc=d3e32022-110900"
  },
  "r424": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "17",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=118261656&loc=d3e32136-110900"
  },
  "r425": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Subparagraph": "(a)",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=118261656&loc=d3e32211-110900"
  },
  "r426": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Subparagraph": "(b)",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=118261656&loc=d3e32211-110900"
  },
  "r427": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Subparagraph": "(c)",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=118261656&loc=d3e32211-110900"
  },
  "r428": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "20",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Subparagraph": "(d)",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=118261656&loc=d3e32211-110900"
  },
  "r429": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Topic": "830",
   "URI": "http://asc.fasb.org/extlink&oid=6450520&loc=d3e32583-110901"
  },
  "r43": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.6(b))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r430": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(a)",
   "Topic": "835",
   "URI": "http://asc.fasb.org/extlink&oid=6450988&loc=d3e26243-108391"
  },
  "r431": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "835",
   "URI": "http://asc.fasb.org/extlink&oid=124435984&loc=d3e28541-108399"
  },
  "r432": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "835",
   "URI": "http://asc.fasb.org/extlink&oid=124435984&loc=d3e28551-108399"
  },
  "r433": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "835",
   "URI": "http://asc.fasb.org/extlink&oid=124435984&loc=d3e28555-108399"
  },
  "r434": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Topic": "835",
   "URI": "http://asc.fasb.org/extlink&oid=124429444&loc=SL124452920-239629"
  },
  "r435": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "30",
   "Topic": "835",
   "URI": "http://asc.fasb.org/extlink&oid=114775985&loc=d3e28878-108400"
  },
  "r436": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=123408670&loc=SL77918666-209980"
  },
  "r437": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=123408670&loc=SL77918673-209980"
  },
  "r438": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "842",
   "URI": "http://asc.fasb.org/extlink&oid=123408670&loc=SL77918701-209980"
  },
  "r439": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "852",
   "URI": "http://asc.fasb.org/extlink&oid=124433192&loc=SL2890621-112765"
  },
  "r44": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.8)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r440": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "852",
   "URI": "http://asc.fasb.org/extlink&oid=124433192&loc=SL2890621-112765"
  },
  "r441": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "10",
   "Topic": "852",
   "URI": "http://asc.fasb.org/extlink&oid=84165509&loc=d3e56426-112766"
  },
  "r442": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)(2)(i)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107207-111719"
  },
  "r443": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)(2)(ii)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107207-111719"
  },
  "r444": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)(3)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107207-111719"
  },
  "r445": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(bb)(1)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107207-111719"
  },
  "r446": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(bb)(2)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107207-111719"
  },
  "r447": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(bb)(3)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107207-111719"
  },
  "r448": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(c)(1)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107207-111719"
  },
  "r449": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(c)(2)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107207-111719"
  },
  "r45": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02.9)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r450": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(c)(3)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107207-111719"
  },
  "r451": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)(1)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107314-111719"
  },
  "r452": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)(2)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107314-111719"
  },
  "r453": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(b)(3)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107314-111719"
  },
  "r454": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Subparagraph": "(c)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=121570589&loc=d3e107314-111719"
  },
  "r455": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "30",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=66007379&loc=d3e113888-111728"
  },
  "r456": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "30",
   "Subparagraph": "(a)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=109249958&loc=SL34722452-111729"
  },
  "r457": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(1)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122625-111746"
  },
  "r458": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(2)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122625-111746"
  },
  "r459": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(3)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122625-111746"
  },
  "r46": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a-c)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=SL7669646-108580"
  },
  "r460": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(4)(i)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122625-111746"
  },
  "r461": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(1)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r462": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(2)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r463": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(3)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r464": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(4)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r465": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(5)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r466": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(6)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r467": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(a)(7)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r468": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(b)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r469": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(e)(1)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r47": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(e)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=SL7669646-108580"
  },
  "r470": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(e)(2)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r471": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "50",
   "Subparagraph": "(e)(3)",
   "Topic": "860",
   "URI": "http://asc.fasb.org/extlink&oid=125521744&loc=d3e122739-111746"
  },
  "r472": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "910",
   "URI": "http://asc.fasb.org/extlink&oid=123353855&loc=SL119991595-234733"
  },
  "r473": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "310",
   "Subparagraph": "(b)",
   "Topic": "912",
   "URI": "http://asc.fasb.org/extlink&oid=123371682&loc=d3e55415-109406"
  },
  "r474": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "330",
   "Topic": "912",
   "URI": "http://asc.fasb.org/extlink&oid=6471895&loc=d3e55923-109411"
  },
  "r475": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "350",
   "Subparagraph": "(a)",
   "Topic": "920",
   "URI": "http://asc.fasb.org/extlink&oid=120155617&loc=SL120155628-234783"
  },
  "r476": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "350",
   "Subparagraph": "(b)",
   "Topic": "920",
   "URI": "http://asc.fasb.org/extlink&oid=120155617&loc=SL120155628-234783"
  },
  "r477": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "350",
   "Subparagraph": "(a)",
   "Topic": "920",
   "URI": "http://asc.fasb.org/extlink&oid=120155617&loc=SL120155638-234783"
  },
  "r478": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SAB Topic 11.L)",
   "Topic": "924",
   "URI": "http://asc.fasb.org/extlink&oid=6472922&loc=d3e499488-122856"
  },
  "r479": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "20",
   "Topic": "926",
   "URI": "http://asc.fasb.org/extlink&oid=120154696&loc=d3e54445-107959"
  },
  "r48": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "10A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=SL7669646-108580"
  },
  "r480": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "25",
   "SubTopic": "20",
   "Topic": "940",
   "URI": "http://asc.fasb.org/extlink&oid=123384075&loc=d3e41242-110953"
  },
  "r481": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.9-03(11))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120398452&loc=d3e534808-122878"
  },
  "r482": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.9-03(13))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120398452&loc=d3e534808-122878"
  },
  "r483": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.9-03(15)(1))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120398452&loc=d3e534808-122878"
  },
  "r484": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.9-03(16))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120398452&loc=d3e534808-122878"
  },
  "r485": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.9-03(23))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120398452&loc=d3e534808-122878"
  },
  "r486": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.9-03(6))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120398452&loc=d3e534808-122878"
  },
  "r487": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.9-04(15))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120399700&loc=SL114874048-224260"
  },
  "r488": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.9-04(22))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120399700&loc=SL114874048-224260"
  },
  "r489": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.9-04(26))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120399700&loc=SL114874048-224260"
  },
  "r49": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=d3e637-108580"
  },
  "r490": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.9-04(27))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120399700&loc=SL114874048-224260"
  },
  "r491": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.9-04.9)",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120399700&loc=SL114874048-224260"
  },
  "r492": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "235",
   "Subparagraph": "(SX 210.9-05(b)(2))",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=120399901&loc=d3e537907-122884"
  },
  "r493": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "320",
   "Subparagraph": "(b)",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=123599081&loc=d3e62557-112803"
  },
  "r494": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "360",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=124429447&loc=SL124453093-239630"
  },
  "r495": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "470",
   "Topic": "942",
   "URI": "http://asc.fasb.org/extlink&oid=123599511&loc=d3e64711-112823"
  },
  "r496": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(16))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400017&loc=d3e572229-122910"
  },
  "r497": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(a)(1)(b))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400017&loc=d3e572229-122910"
  },
  "r498": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(a)(12))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400017&loc=d3e572229-122910"
  },
  "r499": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(a)(15)(b)(1))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400017&loc=d3e572229-122910"
  },
  "r5": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=124098289&loc=d3e6676-107765"
  },
  "r50": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "14",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=d3e681-108580"
  },
  "r500": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(a)(16)(a)(2))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400017&loc=d3e572229-122910"
  },
  "r501": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(a)(23)(a)(3))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400017&loc=d3e572229-122910"
  },
  "r502": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(a)(23)(a)(4))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400017&loc=d3e572229-122910"
  },
  "r503": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(a)(25))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400017&loc=d3e572229-122910"
  },
  "r504": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "210",
   "Subparagraph": "(SX 210.7-03(a)(8))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400017&loc=d3e572229-122910"
  },
  "r505": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.7-04(18))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400993&loc=SL114874131-224263"
  },
  "r506": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.7-04(22))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400993&loc=SL114874131-224263"
  },
  "r507": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.7-04(23))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400993&loc=SL114874131-224263"
  },
  "r508": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.7-04(3)(b))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400993&loc=SL114874131-224263"
  },
  "r509": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.7-04(8))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400993&loc=SL114874131-224263"
  },
  "r51": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "14A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=SL7669686-108580"
  },
  "r510": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.7-04(9))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400993&loc=SL114874131-224263"
  },
  "r511": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "220",
   "Subparagraph": "(SX 210.7-04.3(a))",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=120400993&loc=SL114874131-224263"
  },
  "r512": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4H",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "40",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=116884468&loc=SL65671331-158438"
  },
  "r513": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7A",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "40",
   "Subparagraph": "(d)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124506351&loc=SL117782755-158439"
  },
  "r514": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13H",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "40",
   "Subparagraph": "(a)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124504033&loc=SL117783719-158441"
  },
  "r515": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13H",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "40",
   "Subparagraph": "(c)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124504033&loc=SL117783719-158441"
  },
  "r516": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "29F",
   "Publisher": "FASB",
   "Section": "55",
   "SubTopic": "40",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124504033&loc=SL117819544-158441"
  },
  "r517": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "40",
   "Subparagraph": "(e)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124501264&loc=SL117420844-207641"
  },
  "r518": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "40",
   "Subparagraph": "(f)(1)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124501264&loc=SL117420844-207641"
  },
  "r519": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "40",
   "Subparagraph": "(f)(2)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124501264&loc=SL117420844-207641"
  },
  "r52": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=SL7669619-108580"
  },
  "r520": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "40",
   "Subparagraph": "(g)(2)(i)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124501264&loc=SL117420844-207641"
  },
  "r521": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "40",
   "Subparagraph": "(g)(2)(ii)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124501264&loc=SL117420844-207641"
  },
  "r522": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "40",
   "Subparagraph": "(h)(2)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124501264&loc=SL117420844-207641"
  },
  "r523": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "80",
   "Subparagraph": "(e)",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=124508989&loc=d3e19393-158473"
  },
  "r524": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "825",
   "Topic": "944",
   "URI": "http://asc.fasb.org/extlink&oid=123600520&loc=SL75241803-196195"
  },
  "r525": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12)",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611133-123010"
  },
  "r526": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12.2(ii))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611133-123010"
  },
  "r527": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12B(Column B)(Footnote 2))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611197-123010"
  },
  "r528": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12B(Column C)(Footnote 2))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611197-123010"
  },
  "r529": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12B(Column D)(Footnote 2))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611197-123010"
  },
  "r53": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1A",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=SL7669619-108580"
  },
  "r530": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-12B)",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611197-123010"
  },
  "r531": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5D",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-13D)",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=SL120429264-123010"
  },
  "r532": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-14)",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611322-123010"
  },
  "r533": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-15(Column B))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611379-123010"
  },
  "r534": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-15(Column C))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611379-123010"
  },
  "r535": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "7",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "320",
   "Subparagraph": "(SX 210.12-15(Column D))",
   "Topic": "946",
   "URI": "http://asc.fasb.org/extlink&oid=122147990&loc=d3e611379-123010"
  },
  "r536": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "310",
   "Topic": "954",
   "URI": "http://asc.fasb.org/extlink&oid=123364037&loc=d3e3115-115594"
  },
  "r537": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "310",
   "Subparagraph": "(c)",
   "Topic": "976",
   "URI": "http://asc.fasb.org/extlink&oid=6497875&loc=d3e22274-108663"
  },
  "r538": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "310",
   "Subparagraph": "(b)",
   "Topic": "978",
   "URI": "http://asc.fasb.org/extlink&oid=123360121&loc=d3e27327-108691"
  },
  "r539": {
   "Name": "Exchange Act",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "12",
   "Subsection": "b"
  },
  "r54": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=SL7669625-108580"
  },
  "r540": {
   "Name": "Exchange Act",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "12",
   "Subsection": "b-2"
  },
  "r541": {
   "Name": "Exchange Act",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "12",
   "Subsection": "d1-1"
  },
  "r542": {
   "Name": "Form 10-Q",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "308",
   "Subsection": "a"
  },
  "r543": {
   "Name": "Forms 10-K, 10-Q, 20-F",
   "Number": "240",
   "Publisher": "SEC",
   "Section": "13",
   "Subsection": "a-1"
  },
  "r544": {
   "Name": "Regulation S-K (SK)",
   "Number": "229",
   "Paragraph": "(a)",
   "Publisher": "SEC",
   "Section": "1402"
  },
  "r545": {
   "Name": "Regulation S-K (SK)",
   "Number": "229",
   "Paragraph": "(b)",
   "Publisher": "SEC",
   "Section": "1402",
   "Subparagraph": "(1)"
  },
  "r546": {
   "Name": "Regulation S-K (SK)",
   "Number": "229",
   "Paragraph": "(b)",
   "Publisher": "SEC",
   "Section": "1402",
   "Subparagraph": "(2)"
  },
  "r547": {
   "Name": "Regulation S-K (SK)",
   "Number": "229",
   "Paragraph": "(b)",
   "Publisher": "SEC",
   "Section": "1402",
   "Subparagraph": "(3)"
  },
  "r548": {
   "Name": "Regulation S-K (SK)",
   "Number": "229",
   "Paragraph": "(c)",
   "Publisher": "SEC",
   "Section": "1402",
   "Subparagraph": "(2)(i)"
  },
  "r549": {
   "Name": "Regulation S-K (SK)",
   "Number": "229",
   "Paragraph": "(c)",
   "Publisher": "SEC",
   "Section": "1402",
   "Subparagraph": "(2)(ii)"
  },
  "r55": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1B",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=SL7669625-108580"
  },
  "r550": {
   "Name": "Regulation S-K (SK)",
   "Number": "229",
   "Paragraph": "(c)",
   "Publisher": "SEC",
   "Section": "1402",
   "Subparagraph": "(2)(iii)"
  },
  "r551": {
   "Name": "Regulation S-T",
   "Number": "232",
   "Publisher": "SEC",
   "Section": "405"
  },
  "r552": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "65",
   "SubTopic": "10",
   "Subparagraph": "(a)(3)(iii)(03)",
   "Topic": "848"
  },
  "r56": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124509347&loc=d3e557-108580"
  },
  "r57": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124431353&loc=SL116659661-227067"
  },
  "r58": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124431353&loc=SL124442407-227067"
  },
  "r59": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "5",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124431353&loc=SL124442411-227067"
  },
  "r6": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=124098289&loc=d3e6676-107765"
  },
  "r60": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "6",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=124431353&loc=SL124452729-227067"
  },
  "r61": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(210.5-03(11))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r62": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03(10))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r63": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03(20))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r64": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03(24))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r65": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03(25))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r66": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03(8))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r67": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r68": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03.2(a),(d))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r69": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03.4)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r7": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "3",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=124098289&loc=d3e6801-107765"
  },
  "r70": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03.7(a),(b))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r71": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03.7(c),9(a))",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r72": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03.8)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r73": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-03.9)",
   "Topic": "220",
   "URI": "http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227"
  },
  "r74": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "11",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3151-108585"
  },
  "r75": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "12",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3179-108585"
  },
  "r76": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3213-108585"
  },
  "r77": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "13",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3213-108585"
  },
  "r78": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "14",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3255-108585"
  },
  "r79": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3291-108585"
  },
  "r8": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=6361739&loc=d3e7789-107766"
  },
  "r80": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3291-108585"
  },
  "r81": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "15",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3291-108585"
  },
  "r82": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "17",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3367-108585"
  },
  "r83": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "24",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3521-108585"
  },
  "r84": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(e)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3536-108585"
  },
  "r85": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(f)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3536-108585"
  },
  "r86": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "25",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3536-108585"
  },
  "r87": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "27",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3581-108585"
  },
  "r88": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3602-108585"
  },
  "r89": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Subparagraph": "(b)",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3602-108585"
  },
  "r9": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "S99",
   "SubTopic": "10",
   "Subparagraph": "(SX 210.5-02(12))",
   "Topic": "210",
   "URI": "http://asc.fasb.org/extlink&oid=120391452&loc=d3e13212-122682"
  },
  "r90": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "28",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3602-108585"
  },
  "r91": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "45",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123570139&loc=d3e3044-108585"
  },
  "r92": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "2",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123431023&loc=d3e4297-108586"
  },
  "r93": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "8",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "230",
   "URI": "http://asc.fasb.org/extlink&oid=123431023&loc=SL98516268-108586"
  },
  "r94": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "1",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=123372394&loc=d3e18726-107790"
  },
  "r95": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(a)",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=123372394&loc=d3e18823-107790"
  },
  "r96": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(c)",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=123372394&loc=d3e18823-107790"
  },
  "r97": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(d)",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=123372394&loc=d3e18823-107790"
  },
  "r98": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(e)",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=123372394&loc=d3e18823-107790"
  },
  "r99": {
   "Name": "Accounting Standards Codification",
   "Paragraph": "4",
   "Publisher": "FASB",
   "Section": "50",
   "SubTopic": "10",
   "Subparagraph": "(f)",
   "Topic": "235",
   "URI": "http://asc.fasb.org/extlink&oid=123372394&loc=d3e18823-107790"
  }
 },
 "version": "2.1"
}
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>ZIP
<SEQUENCE>57
<FILENAME>0000874015-22-000104-xbrl.zip
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
begin 644 0000874015-22-000104-xbrl.zip
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MIR\/GT7)/%E4!9H^0G-?GL _9AGFB&%,\2$QYYKWVD08M1.['&=5V6G^87R
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M3A59;@&L5X LWC&-6BW#Z_HAT'?O$YVYA?-OYL(@+G.LD!&P2H6Y6PQ_3J[
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MUJJ_/48>>;3QZU[FYP,;Y\-E6X6J\3QHIP,;LXQ20EQ)&H;"3"/4KR@5@CQ
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M/'YMJJOVCK;&Y%PQ*1B1DMQ5(V:I<;PDN>@"+=+&)+=5E^O,27+"X??W^GM
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M4TEB-2IW-M2*7GLW,"35K+^ !:#+ZD93CL,^L''(97&Z3"E&KY:DA65UUH/
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M_NEQRVA7='O^@=SI!QMW^G+N=- V%RU]/7R.DH@WV$8C>#\R_9$0%A6SGG_
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MQHHX8NREGJT;L1W3@/\C)1^R7*X-&$O1C1FXA%G"=Q,"G,=VSG8+N*@<_])
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M0B]_YI0=Z!V:+\P)! XGV6"Z#NX%TU,++KF:!.M%5]KI,?4IXWOWOY'@O\"
M0']@SK(L=%LG7.EO(!2+X.?P+MC"9W:Q,\,N_KL(AN/=H']X2B4Z\*[^X<EV
M[W]6:'$?B,6-\]/@/N?4U91!X!!Z$:?8/ST^)/S/D+7R[9[W$]#5<^P#)U7%
M;^/"2F(SPNG>K!%N%&$'VSV@CCE6 .$P[L^#K<>DEIZ]O3BKJ?GF-C5S,A :
M5PH58YH&6!I8%V&Q-/3J7OKT>3H=1"!TYG0;;+,IG ;=NO0N<QA82964%/3
M=H DEBM)+A>08HT?CNA&B=0DM0V6+JD<%Y-MC1;B5/33Y2.5M_5?6F.D<0-E
MN2\^N3P5$UO)H)#ZZ]=L"L%Y+K%F=G"?P+GB\\I8FW@_ZY?4NY UWO&:R]+P
M3%M8.@1:I2_H#K,TX<G L9#*)JI$--*8LHS%$L)*_O".D.<TX&C;EL$X"$S3
ML$6D)K- LXNT(YPM[OHPLXM$^M&ZG91B'DMLK:%2$;>V1;[A:I]_5N8<<*N
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M'U4;YLJW&GQ[&R:5=X\C9F^8 ']$]Z8M"DKU494SWDJ37+:D)XQNXT*CMB
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MG_<-*<+G8J>_;TW4A>9W?T\1?<._I^@FK?O$W\_ /_^3H.^_^PM02P,$%
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MW\VW+MX#?NM2"Z#^-F_9\,>^.'SZY!]02P,$%     @ 9XFD5+L>=ZKG*@(
ML4@9  L   !F;W)M,3!Q+FAT;>Q]ZU?CQI;O][O6_1\TG,E,LI;IKJ=4U4EZ
M+1KHA)ENX&!RSIS[):N>H(F1B"1W-_GK;Y5L@P$;#,BV9*IG3O!#EJIJ[]]^
MUZZ?SJN+0?3M8I"5[[[)8I#^O'5>59?OWK[]^O7K&__)F[PX>XL P&_3K*Q$
MILS6^/I!FOWQP.7^:RG*Z\N_W;O^*ZZOAISSM_6WUY>6Z:P+W6WAV__Y_*FO
MSLV%V+X['O]X??/#Z='$;T=?3BY-RYP@F#PTV=$5US_X-N]:Z!?&#=[\SX>3
M3S>75[.OO[GT;56(K+1Y<2&J-,_\G>@V0-LHGKK)=FG4K1NY]V_.\B^/WH=M
M8SBYS[#</A/B\OH^5I2R'LSX"_<3!+<!G/J)-G?6<?)<]T5]^9_D^NY5,7<9
M^5OW[>1"E0^SJKB:?=_QE_6]KW\P+ J3J7F_&'][ZR>92%4Y^_KZJUL7EZF:
M?:G[XO:%U64QYTKWS:U+S3=U/OM2_\WMNQ;5?9*X#V>1HRJVJZM+4\Y>:??U
M6_^U_R7PO[QYB..(FQ^Y-VEY>2X<J[Q1^86_' %\_9CYV/1"8NO]__T_/YT;
MH=W?R/W[J4JK@7G_T]O1W_&'_[:]'7U*E<E*HZ,J?Q<=^&=&Q_5#E1E6J1*#
M<G1Q_6\O5\,+DU61*HRHW(^&99J=1?M[O^R<V-0Q^9G[]<F1>VDB]@:] 6_
MU*]W\\NK(CT[KR(W4!IM1WY*T8<B%[I(]9F)MK<G([LPE8C\!+?-G\/TR\];
MNWE6N0=OG[J5VXK4Z-W/6Y7Y5KVM)QR]]5-^.Y[S3S+75U%970W,SUO67;UM
MQ44ZN'H7_>=I>F'*Z-!\C4[R"Y']9R^J/^E%I2E2^V-47UVF?YEW$027U8^1
M?\:V&*1GV;MH8*S[1.6#O'@7_0W4_WZ,I%!_G!4.%'I[\M7'^M^/-1UT^B5*
M]<];>_WCCZF7 K^F6IML:S(^[>@\$&YL69X9]Y.?TF_O_#Q,,7I97UV_=!<<
M.@(4J8HR<>%_:M)W.XXBVE/EXT"<;=5/^BA4];L% #%-D-66$QT3B0S!&JB8
M$$N@M>-E_%:=&/OSEJKY"P)8Y3><-A)4/V\YX?9.YOG B,PZCC!;[^L_/[V]
M-:;Y0]RMX5]]3$O'4/\RHMC/])YCH*G1,N/&E"B<8!8[66X85(S3! N##$96
M/'&TVMW]POW@7(NKK?<0.7PN/-H)E]\,]Z/[I)P:+!&&,I PY"A/;(Q8#!5%
MP$* )!4$/S[8]_[5,T=T[+[-]=TQ89!(K),DA@80)KB G$$&$\L2$LM%R/W^
M[XNOT7[F),G5KAM3(08'F3;?_MM<38V&2JX-YC%6DA$ #*,R03P14"4X%MPL
M,!J/+3=VIR$7&I47GN]&2[-C*U-\2 =>(/WSW&3'XLJOWD%Y8I1)OQ@]-5 E
M26R-46Z4FFA )8NU10()BR4A:A%2'N//<T;XL7"/< ,;#W&LPM^YJZ0ICNS1
MI2F<'9"=]<V9'^ T.:6(!3%,2DRY&YJ4ED.N48PE370"%EC :)BEHV]_ Q!M
M1=JH],+!]N>M@\./#A.3,4\&^<B@^TXK&&\BZMW\XM+IC-J"V2F<07-F_.@_
M7-U<,E[QG:^BT/5__F%*/]$3+_Y+1R6G="IQ-BT L!'02:8$,.YH 0%W')Q@
M*)S$2APG/<Z_O]</\@IBYUM:_NX>4@L$9W/6XRH_&[_JO__B!EP9TZ]$-2SK
M*_>_&>5TW1=S9*W3AL7XPO&0ZTOJ.WRX-_GZ@>Y^SL0]/2^,&?WRULH#/+WR
MV+'U&XQQR]9>(AEK:5A"DYB8A$FNE $.N5X4QUJW?.V/LNZN/,50\413@3DQ
MV#)!"25&:8:TEOQQ\;-FKO^:OWCE9XCQS^);>C&\\$:?O_BS&W3AU,U(NI_X
MI<?3A@Y$2M%$6;=V1"/(A(H5BBT73DTG/%E(A/\KGB?$;X]OPAA[1E8'SJ<M
M:L4\&>$=H\9),<MQS*76EB0<RT1!*9B-8Q9SJQ\7XK_??DQ-%;<J7TQ1I7)@
M^B9+\^(PKTP)QNPU)H>W+^)M0+8Q:'Y:BDI$B>8QT(@@C1DPB8$64ZV83(QJ
M<EH0T?LS(]NS+;JWM\WEPECCW4Y3OO_)1RS>E74LPHTJJB,8[YS,MB.6VYX,
M[<VWTHF[T=?>3?MYJTPO+@?.Y/WI[>U[C!XW_8SZ;9D/B_I=':%Y-UZ)>O%F
MLM[X.E,;5)-WJ?;O;6J*J'Z>F1E7V#WX[]MFTMT?OY]\=/ONES6.)N_*2A25
MIW!MDWJ/%,#)[VZ^NQZFGKH4UT2X_<WD_>0A;V^MP_QE(8BU8#%&8:IJ/#^R
MC=CUC<;?/'=^[2#V[?E-T^]E\X,0M6U^<"(D&J/?\Z7Q<M=EC-61$S%ZJ]W#
MOET.4I6.QQ#IU'U;.EDW3]C[Z6R]K_7O(I/ZZ>W,YUPOZ/5PULV5@6K+I]I:
ML7;?1-@,PMV=UR8B+M"N3;B[;:0?%[D>JNJHZ)OBBW,1QW0<#(3,?=SJB]DY
M*TSM!9^8+R8;FG;2L"RJ=[/F<DW!1V?4)/5:86[#:U+#0.K5D!HN3FJX1%*W
MP$9OQ;(L).SZEVE6B+_$27XE!E4ZB:9UC.OGS.)U"K7]RX'_65&:[+_R-*OV
M'/@'^677)=NBT]IT\3:;Z*,B!Q_6SO11=6Z*;@/ZL>EL')$7$M8GIC2B4.=N
M438$U O,:..$^$*D#GCN-I$7$MK!^-HX$1V,K\W"\4)$'W_8-<I.(G^WAK]Q
M%%Q($@<*MECP+D3!8!MO JD7#-!?7)A"I6+02;K>'?[KE+B!B.U&(JC3G+Z:
MLLX@[/\Y]-7P^<5EGKFWHP++':U37^<H!L<BU0?9KKA,J[82]+K>]:$IW:C4
M!^>VI%PG:#+7N0@!/1?G6;_*U1\;0;1[\^D"H6! VLJ1UFA5P4*B4JGAQ7#@
MMQ36\2__=6'._9)],0>9RB]::J0^E9B+SG-3D!E$: L0N) (#0A<"0)73M@3
M4XDT,WI?%)G?G[T15)P]J2Z0;!%M&$C6*CT'VK>UH5D]?B<@$31Z8RS9BEC%
MT^@;?*G72?>@=%X+I8.IOT13OQ7\<#=/%/BA'?S0EC*-H DVM;#NB<@/MMZK
MI'OPX;I'WT#53NQ_#@IV%?&]9K>L!Y*M)(J^8I0%MV8U&:WFL=BN6'NCC!LB
ML.NH9EDU 8/D65$N?<6$#19V"P@5 ANK%Z$-NT@-M3AM)QE;TYZM)8&+YAJ_
M;@:]E]D9K!4DAQ!,LI%UL=/,#2X'>89!/)KJ[[Y[]9&=:JI=7_(AS<],-M6R
M*<\.S=<=-_W2GUCRV6BW6IDI/^;%J3^.Q/_PR/8O1+OY9>9DQRSSPBG/9:5'
M!_?(?IYI:BTQ6PK!PMG26_5/C67/:WZ=S8T[#N'B+Y,9)6[19VKO=W?Y;N')
MM2-5WB#QP;6P @\1?Y!=#<3%K;7I,+7GSF9IY 6+8QLT2=Z%=LPZZ<8H;R<]
M'Q?,UT/?.$/B+O$6-A/\.7]])]$J<Y:J0S,L\D%^=M5. C_3+'AHBIO&")!-
MA+1[-5](G^2.<+<6J3[.[J/\Y,PE[TT/ZFN]$>5#5GO.IA)E6[L*+<(6+YKP
MLI@$LH5%O;^T03/NCMOQ%&G!-E]:S)WBIMGSD $RD18@QN#WS^)_'1R&995?
M.$MVB@L.,M5.*GNE?W_4M\A[/?8EXAB0A7$,XOJ@H69P')RPU3EAJ^HE'^BY
M!J>Z!2UN:C#OYIF/=XZF?Y*6?WRX^F R=7XABC\F&5-_I/3X?$XA!^/$X:Q?
M7A]UMULXPZ:Z=\7XES.D_NG7O)^>98[DRC'V]7?MYK#'UNY6.G;F(KXL*CA7
M#SVXFL]_Y@/SGE!^*H'Y$ ML7*SJKDP-L.HFK%; XNN ]H9HJQ94G[5"VH#K
M96G+!O@[$>6%EZ71B/*=9?G]8YJ)S'>ZNY/5/LB^F+).T)4'V=Y5)M2P,'U1
M]H=_G>?#DU3FGU)K^BKU9X?NYI\JO9/IG2)W[IVOI1*79EBEJN52=,[D)\'I
M)I=@B:F)]3#2.#D^E&XVOU7I(/7-P?V2955>7-WI GDBOGYVCRK<RY:SQ$,3
MNM<=\OZTNN#;+D*Y09HYY;EA=)L[J2Y0;9P #'A;!>66L*<JX*UK5+N7>G<W
MJ*Z.!^Z>3M'[*M>Z9_>4[_EAF+I996<M)]WC,[GQWVY/:>.<IT#;I=!VN7L=
M%R["A9M8@7M[4DLS7=9'M5 ZW2+:W56#.U]%H:^%XO[%Y2"_,J;>@W-T>5.)
M]_LOA7NF_T)4PU&<M7\N"O-!E$8?BZMZP6[23I/[M)O>M^9^(T;G+L++0ZSW
M5O'FJ8LOY\8I[;O]PEXS3RZ70U8/C94FMY98[/D 3[:;H1:A9) K@8:=Q.%#
M(G$DGLJ10-7'[J'%:?Y?(AN*X@KZ^W6*YK4=VL!T-P[D33'(43:]6,[5/CTW
MA1&V,L4F,\JCTWYE#.,<.IL7%R)3IE[$<JZMN?_-J&&5?C%'UJ9JLER__\.4
ME3\Z^3;W^?)W1[BZ7F+T0'<_QRZGYT7;+=*I"<VR11>8V=+,T3G$6HJ?YBM4
M9I,\(&29"#G*-A,?U_-J"[>N&HP!'4WHCZ]YN]&Q:LG]7&TU6<>VH#&@8]9R
M!2X///88CYTX"5"DRODV=5SDMRRMRI/^;\^*&7_(W9V/[%Y:&%7E$Q%]XK^N
M?_LYS=*+X44[F=-SQ/501PQR:[Q+8<-'W<^92[HTH^1!9@C 6!XPQ+?V F,I
M//,L.$ZO4A?@&( 1LHS+SS(&H=V@/]D1F;Q\Z1AL],WDZF""A]A?.RH*-C6Z
M\3IY;'T5#T^H@6LKRZRS?FRY^WX6@GS'R+(":*V2* _Z#QTCS<I\H57MNPKX
MZ:[Y\X(P2L<H&D(0P?C8''J.#C^Z/M#E4ZY&"? Q:HTHU/F>^6(&>;VW<"?3
MQ^[2K-K_YI/E;1?*#\QNTIEVX3F^:E;HF\$@S<Y^,9DIQ, W/]$7:9:6=9^G
M+V8#N.$ZR/V4F;YJGMC-2W^DAQAL!-WOS6;C:'LW0A7PWAZ\KRNB]!2>".9
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MK9'84%I+(+5"P%@,&;$P%D A2X"!R!EGRJK-G'5,D.(Q@PQQX4:/&'!XCF-
M*43"*')77SLEKAF--<.<8*K=.Z23! EDA/=2.S)K9(6UF"=8 6>%>\H3'SG3
M&(-$*L,V<];2^0\0&>JF;!W9M71"G%E+.4XL-<F]"!)0UCO>U'DI1#,FE7/7
M@#/"G4A$ '5EUHFSNSF#G+O).\.,<<X2JV/@%#8$";M+ZPV9M<$62*>CD?L/
M@=Q1'#A?PB;0S4,YT75GU@F1[A]-$."*6(IY#"37B<($,V.\*=>)62M$;>S$
MEV-F[!QJI[42@AS.K?>7A;QKD:Y@UJ-/RGQ8*%..WIX;IR%\#E"G7][_W__S
MD_L3J8$HW:CV^L<?C\69^;6^9&O\[?N?9!&]O?G!] _+ZLJ/SN>#M\4@/<O>
M13ZU;8H?(YMG;JG$13JX>A?]YVEZ8<KHT'R-3O(+D?UG+ZH_Z46E*5([OKI,
M_S+O(L@NJ_$'7TUZ=EZ]BV0^T#^Z"9X7DR?*FG[OHBS/S(_1Z-VVS*LJOW!W
MN/P6E?D@U9$<"/7']?=5?ODN(G>_/!\_!(++;S]&*A_D[KY_L_4_]U-WS5F1
M#S.]??>K6;.^$,59FFT/C'5W%,,JO_ZH&#VE_FS+K>=X<7\[/#C=WXOZISNG
M^_TVK/&_;6\?GQS9=& \*QP.?36"WP1??>=>?P>_^^Z[[>WW_?W=WTX.3@_V
M^]'.X5ZT_S^[O^X<_K(?[1Y]_GS0[Q\<'2Y_"F#>%/XI'/-G9U6>]:*]W0@!
M2OCT<.XR].H7^6->7$1>)#GVK1/^J8HRX2M7M$G?[>6JKB3QFR>VZ@3HR&IP
MQC]U]K\D3)#$.*VBJ(5.6R@M.,/.E1M79C@1,[/N9NL]!-M_KX7 S7,?78;_
M'995:J^60JGO/XOBC^@H,S\\1)]*R(&9#.V%H_B:ZNK<OP'?W0:P1^P-^D']
MS^%T2C)^2LOJU _%?6H&@TNAM>.RG[? Z'UY*=3XO1MT%/U4%?5?_TI/1C]^
M/ )O$'7#\3*[TO,O2_R0ZQ(B)0:3D3HI]F,T?ET+E9>29NO]HZSX]Z$H'!@&
M5R?F,B^J*:[T7FD"K+& 8&*<$X(!H#HQEA+!"&>/<V54%U94/V^ECAJE4>]D
MG@^D& SR2N;?MM[_Q]^^H1BB'^\S[@-+-Q*],Y?N'M7=_*=X_Z5K^???=DY.
M]T\^_2LZV3\^.CF-CG\[Z?^V<W@:G1Y%3FZ>.N$801P=G420?J]_B(X^1J>_
M[D=3(O5:G.[LGOJOH3,G1FBXGK-[4=2*H@;'J@7;7$ [P195YR:ZYI=H5*$1
M[6?:Z,=%WNCJ_5$!VA27Q89K&\?06<Z"<$R9!#I.A.,PQ8P$Z&E<]DZ[NU^X
M'YQK<75E1&&RK?>??9>7",->Y'_SD)1<_S(?G01YV6IY>5J(K$SKG=AW!29"
MAF@!G;./!;%8"6XT41H G4C) &Q*8(*N",S3DYW#_D$M%A>7F!LE+:MK;HE&
MM;:U8QG][O\Y$HQ>M$L"[>87%VGIZZ C[RI$6>TGS!?P^W79\D=WZ<BCF);M
MW$BJH4^^0Z(A%(G&%A+D?&?(()4+V+5.]FS[_17T*6)[)"8?$4WK$:./"D2,
MWC#RW6R\>@$ 8P__!^".R1L,Y]S@KCL]'E:$)I[S@H]XRAC7B]#YWO##_'QB
MSIR2<^BM_ D+4SQ-$+96Q0(Q20B* 4.,.LZFR'@CQB[BJQWD65I&Q^?"R7I5
M'](@!F[T!YEZ\U07KADYX-RU_6]N<O4J1+F-;F8?B3(J+XWR&RETE&916I61
M.J]MP!\6')U;;(>[[!;@1D^_H<ZB8]]Z[QC*WVV3,$_8&X[GXFD-.N 1<#A.
MS8O+<6>'?N5,[MU\F%7%U6ZNI[%"#8TEIU0#%1.#8Z:DT09 A!QP)%+/,(A*
M_[3+(O_BQ^2-^STS$%^%W^DQ"SD/&Y5OX"PI-A*.BTG"KE'N5'P[&.^+4C7U
M[NELW]7&&;%06I:01&A.$5 )Q2S&+*')(CH;XVWW(N8)?H0H8]707G XP5BS
M=^3,N=S9<T7TO\,B+76J:I/.2<IT&@KU9<69R-*_ZO<_;#X3NA4Z.'&6^L7E
M(+]RZW.;NZ+#_,W=19AI#ZQ(>\R$S"8J%/X02[5/+.UH79BR'/_YE&8&3HDD
M+&(:QRIA*E:$,2>'$(D)ES&&REEB"ZB1]\Y(H]$OXB]'/1,Y9554=T53[S$/
M9SRX7??RJ#C-OV93(]0Q50@"00 UA%L@18+<.&UBA(*0VP5&N"N*02F%?NZX
M:CEU5!P[U>ADTK069LH-CQOAS-282 XY2T#BG#)JD'5OGQ.6N*>%=QT+N8NR
M5#Q'#[]4_G63VX]SMXR#_Y=>WK&:"$<)0YP;A32)!14Q!$IIB9P-!87B"S 3
M]Y\THGQG+>V*],IXF;R6/2X<3Z>78A#M?S/*>4Q?3'1DG98QY4(Z=AD,MJ)5
M</P1>09IDQJ=JS-;!#4OIW<*(^Z "R*:8*(U)8 0(P3CSM@E%EF%-98:+ "N
M)+X'K>VYP_B4.Y8Y/L^S^]$Q@:F&1#AYK!$!4#..B2)2 ,0%Q<DB2H-CN.VP
M/@?J*P@;W 0*_N-O#,'DQ]*9+P-SZ2<\CASVO(T\&'H+*G)^FG"STJ95H8/5
M<VW?'X.9^E[O45&OH"F,CBZ'13GT,9<JC]P5M0$-T??R!R\"?31Y1U7O-C;N
MF;RA;+Z<7B1RN6QN/TVK01T><U;=^2@?MI"#!QZ8UT+Z!_(W9):#UZ:U*42-
M\/+JPO'X LL"W_"7^KW8^;UQNY?E<!Q0K3G&?%/GOEMJY'#]]3QUG]R _SG&
MV2.06?[LYFJ]L7R[@DC6H)F."2)$J<18,6B)3I1$5&.CG=%+%8[A0JY2?G'A
MEK!?Y>J/7O3O;P" T;$HHOI0SV?% 9>-T.63PJM?Y 8YCR)C?/9K>$Z1PV!!
ME$J(1L 0JIFTEF-'!PHDHV(A>^C@Z+!_=]7KX< ?6R$'6H"#_3'R[^22F"':
M..['"">$:<5BX@P_A@6P +!X 4_OGF?N9<S$*3]U)L.A*+7X<X25R-?DF2KZ
M]&EW,=_P<>=BI.SK3]+,A_[&*;>0\@EIWL73O->%J+<8"<?/C._>PN9!IGTP
MVD3R*E+GQJ' 'YO@]*^IX_G>K"YNLIW?PQ^B<U'6E0\Z$H.!^])7^7@[_<]A
MZJUT9YQ+,[[ W?/:4,<^^C^J8AF;ZU-6_D0 >!/>?^TK62+MOG4FD[_TLC#*
MU 841%%=OU9&W[O[.7A'Y=!9"N5Y[E.NDRJ2ZEQ4=\?^5=P>95V]4?]X/(<?
M>I'(=/0]&LU1.B'AOI?_ZV;@KZ\O=3_RHQC?QQ<\E?4@ZD&*LHHXB+2X*M\\
M%I;<'1:%\<>I^4=[S5.):EA.QTRQ,=P@BH$1?C>SI!P8;KF2 * 8Q@MHGG_Y
MQFAW%<^W'<>5<X3/E$>VN/2YJ5*MA5!TF$=+N#^8W/\9U4#MP8_G*\=2%VE5
M.28T \=:19YYX3&XBHP3)%?1@=>YC@%\#&]/5"+RI4-WX75S#\^QEWE9W?&/
M3X;N1P30<;7"<+0U)NIOGT;?>\F4_(B<^!I?4)VG=='"I2]:6#;L1D._1I,I
M?W@4*U-+XE=D#)WIJ!6'@A)GCDFHB/+EL58"1!G"?L.XI@$K'<2*XTD1#7RK
MQ4@H9[7XYI".A3S/%%Y2S_S4;XO:GO%%>>$@YIY13.2MXXBZ6V#/JR5W,R?+
M_6:EL^BLR+]6YY.OWS@M9>J1:6/3K"Y5K$/N8X=BWOC&!O[DLD<OF#^^R84>
MZ..+YXQU<F6:C>#OO,MM-%&VTQKVS:8&R2A86R)B@?K/8M<?[Y(75]/E)!1
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M_?O+"L)&-ZME]+$HCHI1]=,_Q&!HCDW1/Q?%= $4X\H(A42L#2-Q3 0FA!@
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MZ;.30 QI0A-I("$$(*Y$@JWE#O)6:SSCE-$&(/] X>'#D ]P#W /<'\!W*T
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M4HKC^?0O'H"D*)DV'5*6*(=3NVE;%DC<GNOON4C)D-0D 01_*'D<P/$VA@9
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M<[T5X&%_^ZNX>XK'(L%6L-NL'KCQ:U%<O9MG-X7YY/^\?'FVD%=9_O+E3["
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M35!S?1YL2EPUN0.I>:P7;,8&P6;M[+-SU'&2I5@O9(,-0C;:V6?7*#;^ZK1
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MSS;OY=GF@SS;[13<-8J/W[.]Z6)FIK;*TWAM-V;3Q,R%N5YD<5KV6VWVO'X
M8$N+9E?KC=,\<\^J?8_@-KW3X'LC_\H^:<5ZN9S?@G1.TD5:7)D)N JNT'U@
ML<KRV^K)UH\-!JAMCI[K8@D] 2"> \*3H,[]2FP"J"!RR74F$.O559:G_W:S
MA^^VL@4CB6TKC7*DTZOAVW,M:G_XY3R+Q=SV;2EYC=E:(Z,O7?,$Z_ZMFB/8
M^4)#.U=&\9[=A$K^]A#+.#!S5F9O5@U'^J9'!]1X74$7!FMI.Q3@VA5(S+5Y
M^"[R9WN*5ZY;7;JT[2$9Z]LZHJL:C9O-WH4$78>.QYR,.Y7JW5N7+M$M[@ 8
M6?=\@-*15@V#36@[GV9;OK8[/',+4YEV31@N]4+G=I]<,P07XN*\V:MU?JB@
M-=[+6<<'.>O:Y4SGJ.,XZW@O9QT?Y*QKES.=H\;OK/MH+!= "1_']K>YA6IG
MBPU6UXCT:-A)=0R#+-OM&.X&C+BJ,)7-:WC264E%)0,R:7$CU1:98'L463PN
M<4F(JW0UKT'"ZE66\5A$(4U2L,,JIR+ DN5W+$3F/")5,D>Y@*T- N1LH>>6
M(^X"P;EN\&7(>01&:J>=B#1W96J!V9:!NK.*^3@834%8KQ43AJ%:5/3B[Q9Q
M/IMMB@-M^L4H^,!U#LWFJ;+&H^'ZJ_+T8"^796>PX@G6;Y=<]9&YUAI@P0SJ
MYN:I;?#N!)8YM74-/=<*M;"]>\R+"UL8,[<OC?4\NW$8]-=2PW 5A]VHPI5R
ML=BDJ]IK_[J9O0.(0?YFC[ZAS@Z_3E<KUVRGJ(!;NS.7H*(L8*/@B)QV8%NC
M'HCC]?(_\T'^YW8QU#GJ./YGWLO_S ?YG]O%4.>HL2<:M!O5GS1P.%W<KPS?
MI:D#'7TOOS$?Y#=NI\?.4<?Q&_->?F,^R&_<3H^=H\;O-_X&$[DT+UQ0T9;A
M"6W6A+%A4VES"_*2M@XE3'IY:/D@#VT[D7:..HZ'EO?RT")_D(NVG4H[1XW=
M1;OGC*5OME9*;ZTS6G+U#29+Z=':>!FL"F^5\;M-UQLM9%6EF-\-#=P$*N9-
M<5I55RMFI:/!_&!TZ_Q20\24_32N _V<6@Y-@&[ +[2)/,T28_:81Y>M)*TA
M9=X.H>NK&VT,KG51A[?7JC+859E9G%D@_%+O: :_76DQ-SLI15X'KN?-29A[
MDN80!5@_;BMNU+VJ7NFFXW"E5U>=I,J>K:YSL&NV80R4]+H* #&V2F:.QEHU
M<!*[)LS6:^[:&F7V8E'&C+@NO:7+RAIJKJ^2Q=%4'6<IFAV-[4.KB,5Y*N)T
M#NUSMYYR_Q->>><[T-UL)R*SOCIFZBX:,S'&;>$D1K9>0?W*IFGI>I>6D[ A
M=]HY'HWEH[] _">$^9I#K)NWP/NNS.D:NT5"B.Q7,,7U BYTM:[JQJQ+*Q0L
MR+7UV95+L]0UVZ03_+'(;A:E[[-J#FSS2,WCE 5'E;D89KRQ2$7E&]5F VQ&
M=V7ZQ^O;*@BA;LTJ5E ^R!STAR_6(S?;/N.R@55Y]+'9Q\9>KA>JX4TN*D\"
MR& M;=AP31IE1S.S(7)=6HS;=\G:A Z,?23;L Z2;-&,:E)-0]+&*W]=V4Y<
M)>'*LD\M<(Y&6]JZSH0EB+I%J^W?978%[-.MB-]-[*US=UROJ[YBEGO9Y!/]
M)<W6Q?;D;*3S5@1NM]_T1M>.%NN,F<\WFU8[>"]TB4.7#+5\I^.'F5%^H+"Q
M]SY;:0_-O#V*B78+YD-^*1:52Q].\:*Q>6>;#.>/,#5CVI>28U9=(+%6J26S
M= $M?:T?OW:Q[/+^L\5B;5'%I8U$7T"NS;59R\O_JOWGMX;M>=!;2GEO#&.R
ME;,"LQ'8Q\AIB4K9S1*0B6UXQQPN_J7(+;)PE=W8+"<W[Y+Z7?! 321UE][/
M;]_LW-US<WFW>B* A-I(UK93/Y!V"FI4+^UK$.;9KA-WCCH.Y@EK[;5%@U#/
M=JVX:Y35BI]OO!VX140.(M:0EC*,;IXMK0BKF)Z31EM9% WJ^N&@P01P 7K=
MFT'0TCT$W3WL.. 2K+;7)@V"E^XAZ>YA^P&81DI=ORV3/+/ZH,,H#DPMO9SN
MR!_D=;^'1KN''<?O#JOMM4F#/._WT&CWL+'[WE_\5+58MKEC4$85LJGO$1]5
M[*CM=F5(:KU-+K.[619E(JCYHXT9W?Z^Q>)TJ=+7P*U3?JU%<W]P3]*6$EN7
MH"S#?DH(T9D:+O[CVFC'$/D!G^_.QJZ]=L9L%2MJ*V:TD\Z^KBV8^S;/*K:?
M,GE5IFQ:V>V=?WA_?O'RW<\O?_E;L8Y_^O35\!SSWUJ]-K:M6#FW0%*FL<)O
M+R&"QZK;YD9I9^)OLE3 KO\/N.[FFKW+2Y?00ER;>P60[ \EG_OH5OZI'/3"
M$L0[\_5_1CAD#%%?\8 0'2B. L03306E2:1PR:C,;?P$N6D2^X@9L8M6F?T)
M!^B?GV^7^D-REEOW KSE[&M:_-,N_W5S@\ZS15J\BW\QF_FZ7MVOY>+>E&O[
MU5HK+\PFI^Z-O_G M@P;-S;XO/B_+U[2%UYAKIU9H/G)7AI#I.G7U0^+];7*
M5N4W7_P4A98;-?;E)V@L-8<-NGLAW/W) "7V_G<M\I7#^6&193R1:XVM6B]4
M:=N &VI^?R_RULH,-H3,7=;*B37H/%6"-9)QB%""B<*"D9A*B56DB)(41=_%
M>;9FOV]B 3=NQ#)JQ$9TN-SRC4<2'G'GR*8$XF](($93 O&40/P8A:V7GC<(
M9K]'!>\>=AR@'5;;:Y,&0>WWJ.#=P_8#MH_4=/SU3G?* QN/O4!VY ]"V>^A
MTNYAQ\'98;5]-@D- MKOH=+N8>.'VDM-M8E$UG59-V!"A3>5^[:XIXZ-!3?3
M%9AW%29E=>&-15D]NZ43;*M!^/"K;&D9JVC+J]188ZH)JI<1F6T]9UO'>K&6
MPO9%JF<+D+6&U=3K!Y1MO2B!V=5M-;_\/I^NV0:SC*)"8E=Y>GGIE-5B,Z%7
MWD5JIBGR^>VLK&+D#@"*^GQI[YM[[\9D8)W8U)0R0<2KR@/9-;J$CJU(HDM
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M,;6Y$&3K";4XUC-%#E2[R)S:7 BR=:TM-N@J(@>3$(<Y?%V*E.+.[Y"P5[6
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M(C9ZST60.#(DF%D+I[MC0%X@AUP07' BF=).!TVQE8)H;1#65XJ D,JNA^D
M>L5&GR0JC]OY[_%&__WV\VEQJ&>*RN-V_GN\T7__Y+5>Z 7.TJ)V*P\7-[=0
MEJKH>94L=E=6<?2SGEI$W$-5R=',]\HY6OW"=J^95%:$9[F&!;[<^]?<3&:I
MW+^LG,AIKC=AE+3]*H9>N3P*LW_)U5$[K.M\LN1"*-TT6?W.ZJ&K$_AR^#J;
M/K6N6CI+LCUSJFO8SG%+3I*[3]HY3<FVW/U?IN%M?%U9# T9@ZV0/!+C%9?,
M.JNP0S1F#'?#C%F+\+:CC)'181<]TE))YIU2QFAI&3?($!DU/XR,6=-,_&@"
MYI=I-G+J_3R)?"'MG%MDHW-K^]FT.- SR1?2SKE%-CJWGKS6BY4OA\X*SW44
MD["I>F)M7E42'^.,*9 LGJ+\=1%J+O/)APG0!B30)#LBX._A;K8 $2GS:+(=
ME65.Z7<K Y#9^[SLCGGH]HDQE![NA4_\;CQIA MV6509.1B#B!UET0;B+X=*
M"M]-Z0,KO2R/>G!.)?I(.Y<&.4GF,VGG32#;,I]?ET;RNS!Y?P,7]W%[RRL3
M9()CQC@PIJER1"I*M"/*<4K7="K:619J[K04AH3@$ N:*&T,5AC&%!QS=X6R
M\#M0'5VF@Q\&P^R=^&N8]7Y*];BPX[V\Y:>1C^T<$&1C5O3V\VIQR.>2C^V<
M(&1C5O3VM;;8H$O/BEZ?>%A00O)ZIY3>%![M31_<_B,>;SO_ ]GH?]A^4BV.
M]TSY@Z2=_X%L]#]L7VN+#;J*_$%GAFY>9)#E6-@CM[_.!$Q9@Z&7@3FF">@D
M^-_^YM=7Z)N_Y(QWBOL%0$N2) F[.&?0#3X-?)694K\:_I!^+^10\"_,)U 7
M/X;>*.=;)\.L!%?*XT]S;>+,%,@JOJB17J0O%$")+2;?>VS>&7-O"^['JDZ2
M64<#Y,.D/J-28Q6"9(($$QT+B# 94##<J2=H(DWL#M;$[@"./,VHS"]J# ^T
M$<,#O5S30S&O=\]5<H48=9)2H8$,%-+(2&>#$EAKH<B:^EQ<KQ(??I6"/5AE
M/VGP*?\TET>>3$UOYZ&B&U,+M_.<%HSJ3*F%M)V7C&Y,+=R^UA8;=)C4PJ/J
M\ZMJ3*7&GTV1H>T<772CHVO[0;4XW3-E<=%VCBZZT=&U?:TM-NCRL[A^;*>=
M]&MHDTF&4ZN(Y9OTLDE(@?C\%3_P.2)2Q6]\(JY495&J* N\@4I;*5U=R:4T
MG]4)0OY1HNS9X,R\1.\-A7?K<W8W+2H?#9S;BVKHE[WO2_5H-G;_7& OQW%*
MZ\D8"HO';XS/0-O-%U2C)'G_8#I?GXH&VKFRZ,;LG.W7N8U+YTS9.;2=/XUN
MS,YYPF+;;%'A]LK].0[38V6Y!O*A+%TI;ERJLOQI,)U]2%.!3\-P6#8>R?IC
M^CT!/9:_?_NPU5@Y^W+XS*.^6FV1LOP=G.H+'W1 F8WOONDM-ZS9E]7]]C=:
M2+W:,FAY,F8^&S\RF0>;>,J>.#\$.WLSFLXF\^1W?U."'O\,UN?[Y(SW[XI:
M(3 #F^VH$4,*.TRM#4QY^(^VU"/GC,)>B36QS6Q5_&-YL(R,^/UXE#<%;L7[
M,!J,)W]-?GZ$"2]'7@>92)L&R0(Q\079:(@<8R.<<PP+[(*S8$<&;3V)4COG
M Y%2K^E?3"Y@(]!+>.N:ID.KEFA5)^864X-KEN961&,RP,\1=I5XA#'%' MB
M&:5:!>^89S0*[&/07\[U C(CA"H!*]<,,VJ2OT)*XZPSU@IRU=?K/WMY"M^L
M-+MJUU1J#VG>+KI!]XMNM IO8-))\R]=FB>:Z=T$_W$9]RT'\8_ @%#P3(&@
M-S0P;+B.7 :I B5P2RE=@USU3#DQEX+#\C'UVC*$I?::I, ')T0XS]=&L,^_
M$5?&B=N%4>E>8=3UA7M;GZ(=)_[2.?$/E=>F</>4S:+.3D3M@M5TKV#U^HJN
MK4^QCHB^="+Z!63A=)8K85,55@87*.@I2;_"POSY_2_G)ZMV*0YTKQ2']66
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MS_#1O^:YQ>>BU\VV:2O,=]^_1S=NX5_LYZ;'B1W_N@CG%L&M]*KZ#6XRR+V
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MI6V>4$G9QES.__RMJ 8K:BF;Z@:12E.M%4A=PKQT%@4>C3*2J.BB7F,0;U:
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M&&:T<F=P1NP=3V/D)5D33TL'<KG'0*65:>-%5(Q9J26VV!"KM-:PR3NW$+N
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M"I/@6WA7KI</,-ZQ@(X%7  +.'7Y":5$,F*LL82Q:)1UV >ND5<$>^>^)!Y
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MSU@DB.ZNSLI\\EJ9@H*+!@RUBBE)O?:/#I <ITARVHMC+XY=B"CP(!R*I./
MK#!2&^6(]LXK[@PS_LM0D6R@1"<;)1Q)N* 7[\,YX9&0 (X[X1T11#%@40'5
MR4@>2)2/=L*/4H"YM@-E#IS>['N==+T[:8<BF-V)3W8R^OB8=B>:BD2"B-%[
M$2QSUAGT+H1U#G0*M*--GUK#0LT&EA\X6=*EM&LO\\<I\X\.+3!-? R""VI
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M3K3ST3P9(&?#C["(;2"C[,\Q]S+?R_Q3P@N1AQA-!*%M$-$D%T#&/ )4&RI
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MKC.2W.H[\:B$D%% HD$@C@3C@#&U\0QA,]"Q8U<8)?2 6]+C1X\?/7X\? I
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M]YR%P*#C<1?D_#]GZXS_ZS\;/)7.#]SVZH!#Q'L)?S82'@&X(XKQW/K.$V%
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ME!P(>^ *XQZ3>DSJ,2FH2+BEU(<\N<H!$,ZC8* A2DV@C3;R38?8GLN1AU8
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M6X5YOLK$QQCFJQZHL1C.\R !'U??:@'^;(#DH@#/5<+_@M,>O3(=F:,J!=?
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M;+N(?T&=_LH9]8\[+-_86*,.-/I[>,^LDE#=;)C5==WD40VEQ' ?)!&)$"<
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MU91.<@V:__D7PZC^MHA_+O,M85%$\!D'R@9457O3X22T(_ [M6VC^^C;MGD
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M.)J1[A_'3PKX^DL*=@'*4UD'U?2"N2HY-BJ(.@+:0RD@8  WRV^^000[9DB
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MU1;98A/06MKTCND4*6>%^(*>07 (II$@(@:M#T3.AM"UX+D?Q1GH@%$)DVE
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M$R3A4<&B_YHR84L6'/]*E_5H R#QV[M^<))6R1)#.:;K?^;#<)KFEM#@L7X
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MH0]%](DPLQ@'YLANIH:P@EA475"2":,BT+C!6#492S-92 MTP,L=$\J/YJG
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M<#^!<'T9P/^\,HTW?O!!J4)FKV[8^JOAO#';O/'Z4YK95S_N[30GHF5"9O#
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M'#20CQ#I!IO1F01\#WW6; S^A'DP@+?I0U$OCPX1NN,*>4",!\1X0(P'Q'A
MS(;+M0?$/._%]8"8+L5\%_V1F\TK#Y3Q((/'9[A^LV$,UUZ(O1 O"/&ZJ]5Y
MJ(RG:?>(A&>"2/#"]ZR$;W-P6"_. ]*H%^\'>1)M[[IXN=M4N7OQ)52[ZVUX
M8+XW"!>Q6>LMM.T]$2]XG0#2>E#^.MP3#]:O[R8//%[GR'<.UES!RJ/U_:;9
M^$WSNK\&W$O7X/HOBDAZUQ-)/PJPU!-)/WJ"RKWMSZZ7--"9+[ZBP4K>J^L8
M5-/+9+37R%(=EEG&$S[+)/2.%YY2.4HD4!;9%NBY*1%\R@RS/H)$E"D(55YC
M-*^)(+>/@HAY#%=Q@1D7Q'T[2Q3J\ERF+*<JC2,!&@P^:*MH\-3DGG=/'3K_
MJYC.WA\%%^4,^92[F2)TDAI&=LT-W,QYF<$V=VJ?]+2,4#I+SB/3BTODR@+S
M;9!I&D4G9E+DJ4!Z[Y02Q'#)AV6<H(BP/*#ZT.S491$G)!G8#>0TCH4AP78R
M9.P#]#B(F'U(3*$W\9_V(<,LGB"[?<D$LK"YBGFOXIT-<Y/"A/DZ)6?6..)Z
M+?)"(BW^3.6:C#BGI#DPUA+<L[EA<C;K;6;%3%G7LG0ND?V9DFTH%8F2:'+)
M5-3%I,;("_^W;%0^3\?GZ?@\'9^GX_-T-D2N?9[.\UY<GZ?3I6N@S_4$^9<.
M'MODD/.:AO5ZPP!!7H:]##>'M;]A8,J5'TN=.'O.PK"$V0[GCW?JK'=;KAGB
ML^H]L=Z[]74K;R\*]\!RK??&V)OFK:9Y/:+]TDWSYXFOWUXS7M=;TU[L2.Q>
M> YY)S3\29J7&5XW>@.X U;/]III;;T!W&%16*]Z] 9PVRH<JNFL+&06Y&I4
M7&.M700Z)''H[>%G;)B\V2C#Q(O=,Q&[UQLE=MW(<O[F ' QD9G/1W[.::&[
M:]Y8/A_9"QZG/7EFI*[:]9QZO RPZQF0O(G6NJ'W-BQFZ>7N><C=NN."S\,W
M\ Q(WO![(B*:_0TQ_+S@/2O!V_<,2!O(@+3,#?%,1_5=XTE;UDK:\O8YD+;X
M3>,WS7J9CIX!/=A]F8XVDO=E^:G;37X7I(-XAK0N+J_*DQ"\] -D>;!%FZ]%
M[M3O==:VZFA5T9<JW9H4$LUM@05KM4AQJ6>4(*37,!6>;7W<0H:3%/;G>/X-
M["V/M]_:J*=:,VHO9))0@>*?92HSP=,RB*9QBLQ)L%FN9'!<LVD[,D*GZV.G
MZZ+6]5X &^_B9](6@UY%ZF&871K2H&LQ:U:4/%?(S )"<QT7$Q+K62:W*CX@
M0\&"S[9\6B< HJ+46'D<I"C7CS1$CNLNPT9*YSWZAYS.$C67ME0T4JJI\,L$
ME@XZ7I$0]>#,&8ND%TQ*F#IDN8'?ALQ3="7AF8PW W*8])A.)B:>FCXL=13C
MYUA[O49Z [LVOWV"JRDE6APS<S>3XZC1<FZ<&B$.?F?)<LQ\342!_4PE;VTS
M>;@\H<IF2)\C;6'L/$B@K_!+,517D@AM1)(K.\J1I-+,@8+_)U(C3::SQ3 Q
M8A4;@[*F.M2N1KGX?')Z/OCWX"&L-X]&VG0_RANS+SS7S<,H%SS7S:;01GBN
M&\]U\TSI4#S7S3->7,]UTZ6 _QW\#8]"6AD:9)-CFFL:UNY;SZ7CA7C#A7C_
M]4LGT^DN/LK7HWYY,!1?C]H+G\= ;93WLQHDTWVB_;>[-]ZM>4D@=^^)>+E[
M$N?A8,UH;>\\^.0*;]\]6";>/C'"SCL6+U3P=G;6G/W9)<]B<[,K[N.3^(R+
M^E;RX/%UCGSOJ4,7/N/";YI-VS1O=IY#FM*+R+A8 (MV-=4BDKZ4[B-D6M3&
MI\OJ8I%16&.\&AR-XC"6:8@X;1%.8GD%/1QE:DI]''P)I0@^R6PL&0V.'V:U
MRT5=QM0IMJM;)\@ZC+B($:(.OQOEL@B&<S>GHQ65;U'-\*(RH6Y2A_ U8[55
MJ"VP6K] 6T[YWPJJWUK_5Q'4O$P)C]X/'A;AJ$LH"DAM37'E3-UB^*@,X>.)
M%%$("JI :+W0 \(I:YU<7>A63ZZ,VB>UWZ::7E39^SU?]OY1+I3:<H]>>-G[
M.Z=CG5"^#M5F/DEAW\I.#:/6OYCZ9U,;%\]7/C+J9R&EZ'VWV]\V>28UW??=
M?O^-_<(TW#C@4#_V@S/*TFGVI=*L0QF*$C,"90#;(\4$H"!1UZ@AP4R$K0 :
M$I0CY<&H6ENY4;[Z= A5RAE2^ 4=5?<8[2V'-8VE4RM\#T$%;0A39I(#-S<-
M*C8C,0>WSX+R65 ^"\IG0?DLJ,V0:Y\%];P7]_EG077BQNU0I=0]-&E2\-#S
MOZWX\%VYR*[ERF =._SYSDR78+*U+;/S;J48)S$%U\)$'M4(/-$A>*5Y7A+A
M!3%7O'3DZR9?F:V+@6S#4J&\#'L9;@[KQ=.=W\N8>[3*H(V8UDS,*585IP&>
M5[Y@Z(,VT:IW2@?+I'M1>!I1Z&#MV/7D*G0=B&I5*1CV:.2/\?(([Z:8:')N
M&<"9Y2XM1\)@&N OS5VWYJR&#AE3MP65NI2T]$U]W>0JIO>4H:?'DGHA]T+>
M"2%?3[)&%UP*3LAH7I:O.>FB&QO;@4IO=DA@S</;[4**Q).?75Z.-U^.G[9$
MV-WEN)NI"?< F1&L[U)\_0:8V6/"(7^2<,JFZ.MI*'>/8'[8X<.R8'+S?ZAA
M'@Q"PFOO;N^\)4[ZR\-_#) ?_3]E#,=I4(BO,S%'3O="F;LD0LA+ LI@,Y&\
MDHDBEG0^?*,8T=UYH$""@A%F0L[AUWDP*S.\=BJPJ9/SP^!"$A-ZL/-VOQ\,
MDF*BRC&SV?_:O^@'ARH=0S-Y$"/#>HH$^.2\)C"TG#GC->>Z*A/LQD@R+K-V
MY:5'0KV#]R+R/>/^$*G\1%SAI3)RZI<978E1DTRIKZ[B'-NXCI,D&.*P9U(D
M,L)Y4ECB_3K.$6L9Q:-81C"&"@-/C6<R1 6 $,_O=OH[%D"J0:$PMS8,NARL
M&M21F[TZ+G7;:?8F7&JGQ//.V^Q4%L%'E;.XVG_ T(*+"4Q!IP;UZL??49QP
ML5/H:8(]A8WUW9O7_=V%)7JZG)^:^-0Z^NZ@?W 76>JAAH<6,SE*8 ?G]+M1
M@CD=.E4EBO.PS/.JN &"HH<K':'(XY"U3YR4F,QBAX+2D:-T!,^TM@V.FG)Q
MKL'A";[3;]SN[[]9_7NJUM_LK[1U/&+R&1X <'BLI%+-(T"\_BZ"./K?5Q]C
M.$+@4)O#)_^UM35(PXG*MK9^Q.0.^QU-UZ&8Q51[T=0YZ:*&@@-/%UGAC*PJ
M\\HI440):4N/>; G$]C:FN>@JD-2E3'1;VB^@)IULKXR:#0M)7]N*I<$F9J+
MA"JKX(LOCW^^.#XZH;]_'_SKX\EOYX.6-OK!!Y-$!^>KG&G[(".CHGF&FI/?
MI&#,X+#_"F,O0!A!9?>W@Z$]JZL7F.ES1[@PA^:5K#T3:1((=:I=+L,RB^W@
M\%<6C0._3,#HX>P^!.KH,=&) 4N+W:9-/\*X$*KP6X:7B3C7NA$&&$H9D:IO
M#'?7&:[-C+RQZ\WJ/*/[SSQ(3Z:N%^<>7'';&:Y[4Y^20&1@IXUUW9NBDC01
M8 JD1CG5UZ1;UL^*\Y_Q;,6;\Q[]+ZT5N'@T.RA@.>BJ@J?/227J\5RJ(0Q6
MRRW^^%IE7]#$#K4>B^(($9=!.,$I#W*8&3!U0[#AC8HXDJ'$K$6SPCNX)*V'
M8-<6H347IYRB_OL3G1?*^4V+#"_-,#_5G2K:18WA4<$W;H8\APAW>$ 9FI&Z
M)JF\GLBTUM!0<G:85B[Z.7@,/!A,&BM$C.X&-!5F\<P(-V[/J?A#<4TNE=):
M:Z%G>!_GEV/N\!B\[TGN#M3T\F]MD_^BTFSW?9KM"TVS]>EQCYL>UVI-'SK:
M]*Q2@EU(I-O9?B9)*9_%G VC(S"JA_/@,WONM<319Y^T\BUK\VC2_WTN,5J"
M&> B08,UU\?ZD)+"X71^\,+X[*R6E%*\%.ZRI/O5_8;5_8C7 @4X)<$.Q?+]
M0C_3A?Z$?M"&+/1*$3=O]E=8=J[FO.DLL_N'&MJ04L%_!Z>8D1E\/\OB-(QG
M8-MI1/_*CS.?DO/L4G+>[.WV7V]44HZ78B_%S6$]16$J+\=>CKTV7KG)U16[
MJK^S^[K%M,([&@MT?GP[R^?)W7G%7K_N9*:<%X:G29I\ZT7!BX+1"QU,IGZ!
ML8J?RC@A,GB;*SLSER5/=\)NANW\/$OTO=U=<^4E[[-YN8.V]M9<:LZ+G1<[
M].X/-DS=/5?G_LP6)TF0$OX1*3B\G7[WS,DW:T[Z]SY;9V5A?\UDAUX4.BL*
MN[M=E(75>^^/RG_U>"<IYN#6 /5/Z,E[)J"56<0=8@+J0&WF+OEO7LB?HY _
M+?F-%W(OY&L0\O5>R76?TZW5[KLWI]OC&7??A.#W[%==P"VM>7@[O=UW>T_,
MW>B9W+PLKV)X[SPCH9?C9R#'H)/?OEXSJO2YL1)JCH\E9!1$C8<A+LO=8RO6
M5V73F$SF) V$YFTA(A;BL6%"(":$GUMP#/3&?L;75#VB%F'^'^9<P2NL&AL+
MU7AOQN3ZP4KI3HZX!C+26)1I".,3<0I]O(Z+B:&4,M\7\12["-,Q*I&1D E2
M1HFZ1@J/7(6QP'Q<>A0GK$R1L&^<0N<B(N<;RE2.XH*9 I%1K$R).(!J,']!
M?C^1*_QH#G\F,7TG00J0RR8W3!V:/ W^1:_/95$D3$=(+\:?5%18^%J:UK*8
M*,.U<PDS*D<JDPYOT=<P*2--/@0N19XO[WW%SK-,A)@.07.U_6Y)$8N $OLD
MQ5%5#S[)0%%@'\(RRR21P.!/>[#P*'6C+9W:'.03*1M,/=\+3'@&P8'FF-?G
MXO@PR,I$YC^L@O[KZ4@*W?*$1\101$Q@21)<S$!"HDZ-ZM6/Y\R3J4@B;NM[
M(,(0_%6ZK9Z!UQXB;U6<$C(]V.VM<FNWLX9<Q)9R*!A4??FL^Z(%I\<$D=BI
MMVOH5'/6;"\T\0[C]O448YEVI/B,2%-CY(.TCE:AL!/S C[@36)9%YU1(W43
M*1,IPLF"4H=7YD56XN,/(5AZI$KG=]X[YR[#W)'#,(?__E2K6?*A4;.D,QL*
M3M5_E* *F4(7M..LA!&)7#*[V]#@3HE8=J+*7+-+-<NTV/,6I>"[MP?]?<O&
M20<K/-):Q44_L+/?WS8/D!:W!'5T"ND^Z5,)_BBNE5,'A@\C"XUE=C!D+]UV
MNH'BC5$9)O1<VG_;"KP0NE[=PF4@Z-CJ7O_=.SP7,7&<VUHRL%M;VN_O;E<M
M'?'CQ$<:9WGAD@_#C\$>G+@&CC[454KG-]$$1_9L=Z\.-;?A3[7GX6=D5,"D
M#,HQR!?2@+W=Q$W(UZ@+E#Q=VF#&;,7E66+%:.,(-TH!*C6E/5>)/;H][<QM
M5NNZ>P0Z<Q6'V"W#A5=9OUQ/"<0#M#<U.1-98:QN,)*F\&LXJ3)N:5CF8/3D
MG2,A_!U)Y.9LXI&!9R>9NF\)/M% ).6 HTQQ$IG^-R36;4-9AW/H/&]X/:'5
M4E,+\NOB%&S'VIN(M-"E#0=3FDY(?7ZZABH;CFQMTI*E,."*?M2\I!H3*<+*
M6L5-G4;<*^8FO3=SHDLYB0T(M-NUH?Z+NH9Q9SW3#_*OB/5<:K_(<9P2:#DE
M E58I23^PCR@]%4U.T1DG%<>W72JT+)1X9>>_7G##,B16K=Z#_%W?@4'T?R4
M6-Z9RA,AB"B;Y)R \HM!A_X^D=13&(*9(_NXV0J9H;?%IL*)4CFMM!JB,^:,
MD7C3(XEKBT7*KL ]A>,/U7NAD'\=A &\&*NRV4G+RS"4N1VSV3X]S<DNKP2<
M#<1K[YX%,KV*,Y7:_8D_1LLK-J2)E;T%A]87"0LY!O\H0_[2N^[,%T6.^-J3
M(RXYJ)\[.2)]Q,S7)^"8['VB_7(>YU]:^*\;E(HKB1K69>%6NL2:M'T$577)
M;(VWT#NV7*3JWINB5[NSEG@C;/CW02V\NE(^WU8#[>3R^!,8S79'UJ*H]4Z+
MLE!+.KTPD:N,]+;V^_]^'9Q>GEP.+D]^.PX&IT<!?/#1_/OHY.+PX]G%K^?'
M%\'@I[-?+X-/@_-_'E\&YR<7_VS$B[L:E_V=/0@P7U3.%@LS)5.,I'9 +7"K
M,UMV959@_6..9BXQ/#1#L&F$O]'G,QV89,3 XQ-8 _A!0LSTRZP8;3]1H95+
MC&.6&5/89W)6\EZN3DPT+L XTV9VJ+*9L0PY\$*MC+'<BSZ X6@-K5,)AHE"
MXX$,C(!3'W@TQ7R&4HIA1!"8A2DQ=GE4\MM,IVDP^F\G=.I$0K#Q2%$($WJ=
M8,D:+!YSQ7SU]8%9J\GY!1E:Q.KO_,)6?=$6!&S__ O(1IK'C?=#8R 0,=NL
M.(A,I+D(=; 5'<P4G5H2&S1YX*.Z-:.EJ$\AKPPU&+*L@TDVE$DLK[A(#=7A
MP&@T!HPJ5GGT@G V!=E2PS]T0-P13/:/G? 3^TIZ1M&LQ C^""VQB=.R=9AQ
M6IV6T1PW[A#-"9C/\!]RY(GN?]F6Z.$*@\9(M84>SE&4F6I<_Z!:")#\T%Q"
MV'\N+(EY%\5:Q&B$7;QUM3KHF>$TD_?0KEINF3?T2<U-@?DI+%@>1S&LC-F7
MHS(-C1/&[>!7/)U$N6<51(3>8,9;%D4YH>@+[%:W46)!>OM^2;/D8.(CH%^0
MIA\5@NY\;_%%M4)*^%0EKF9C]?3W["A4Y1=0'SGW/"&,8RBU*"#3ZMS(0ZUB
MC=D5]7F-.8KK=*T^T:82#JY6%(]&<0@=PB=FJ.M"T$.#8#*?X932<0P+;()5
MAE+?6<S&&D;LH#G.+M\DX4DB<_0!(EWY"O<CK357'[)[,9Z"M4/EH>\9A[YM
M0[CFX3[1.JLD]\;A$QJ'^YMG'!Z>G5Z>GWV\(,/P\_G9X?$1VH*;8_E-\>89
M[34L=Y7P21[JS4!JB$JN1!33XO.(:CK@W0XK=-B-9:8+SL7I" .'9.;H8]8-
M2>M7D+[ S7QL= 66[V.52G7R3,6Y'K\<:W#UJJH6D;'PX.?ZXELKOB*>5OH%
M+2JJ:&?4XL7QH=;N.=_84CO886T TA#(7'#' ?T185A.2X[GD6:&\[Q,0?J<
M !];0ZAXW(@0W4Y.8CF"L8()0F?V&:I8"@!&^KL/5GOI[WIX]E%)&; 02$6C
MA8+%+VB,8&I&,+B<E'XFQX*,JVJJJZ5D&Y)6B]XGKT12FG/O#BMN+N/MS0\J
M\B4_QJMU5-L8M9Q 3Z\EQ<VTI-#E#QUPN)AXH)F@J[ZYT" $Z10QQ&?P6!!#
MT/1EX7Z%]7]"F+PK$W?#%V5\+&#G D66'<8ENV88#6Q4<*K0B)0AAW6Q#$HB
M^33+\9S%*Q^: V$]'8I!UA 9(3HL;!+ /LB#_RL%;(L,VCNG'8('YP<09GC[
MUO^1\1N*+(L)=('+:43"\4PDF1DP=:F.8)KYU4)D[11;KN5602*!-L )V(_G
MM/]V]L36SNOOY0_TZYW7D?X7!\AISU8>04U9P(MW#O;V>9],J0Q>SWDL+V=X
M\Y&;6T>+4<'H?XR9=6[W5[IU^\%/=&FJ[95J=GL/;1'G5.-D: O><>M2B2V[
ME$NJ_:P4U$0('UT72\H4U8$+ 7 L?_:1Z>H@J0:@,OJ.KQ@XNLXCYDN:>MTF
M[18MMH+6/"A"KI2J[0FN:MCM2DZFYAQ(+AX^I#(;FY.4[ZVS>"5=3Z/R5%AX
M0O(*(F.88QM@6A9&Y_R'U4=U'M)R&F/<SCMN-[PKRVKP,;S_@?]0;*#Q0.^>
MO>4K+S#V2W)X2+4YD]&^U6F*UKS;+W&2G)Z98F,QR@;(RN,M6B$[N&S=K'WY
M>7!^>7+2XMOA%\')2:#)CX.SRU^.SX.3TP]GYY\&ER=GIW?U(<%]V?&^XQ/Z
MCCNK]!V-2#ZZ^_CQ^.?!1_8;CX].3G_>%,>1"WJBNX4H9?BO#:O&Z95*KMC*
M2\ U24S-3HR7VY"J=LDH*HSHJPIHXMZ6]W7E)PZOTRNL T.ZOQ!%6:$*^77:
M V&[.2<+%F%>JD!]#-]76LM$KOO!B3:I[8^H!C/%?5%]-\?AUG*79'0-V7/1
M5_9BB@A/$[5S-*V!54<\76&8E5@G$4'7%0:.3'#S0^I)/W !I'^4T9@N*,A3
M=KQKB5<*,'&F[OO0M(KG(@^)CD>-C7!ZJFU\^@FUVN@Q#(XK0X+/0+4>M3%2
MGQ(\]DPG:#YBA#Q=H;_6"(;2JVEQ:"#4/V?R[70T)I2</I@S!"Q55>E!Z(;:
MY,:T 98LUX,7"+8PD'<$\A0V6L#]JI J[F-<UC*O'J=%P[G)N7"/;.VS _RA
M.6W(3D\#K_"'8+9H;(J!V_=?/&+CC4=LO%S$QMHSDBSJ]377_<7+/#PMRDQ'
M%\D5RQBLAA>2DD&X@R^A%'"4).RF\:VH.=6.0 -<HUHZA+9(:QU.4 GB.2>H
M_BT\]0\U2<$=_P('8B_ -).D'US!2:12T*2?)P*T4"A+,E/@!R=IV#<_ZP6'
M_4$_.%5]ZO+6]IMW.V36X[O1D-W=?F^[,*">]>GCG?><*$::?)9@X#<>C?*%
M;O,SI*"A^R"M\12TX%C@96/P??R#F90IU4RNYL-&5X=*9!2GBN!L(C_^/6F]
M[V-XF$9(_45X)D<G$GU]9GL_DFDD\ Y'=[S99=TWO.3GY_6K3&])?4]$,M)G
MBUU/VGN$I.,Q\$*ZR]N_W_20M\7?FTY3N>1PPICU&/TD\&)C-'.BLM"I)V ^
MI)(;LN[J&4P5%J&&5=T."O%%;LWH+E^Z5^_\PFLV-KCW]?PF:)SO\_A+.,7$
M%(V,:QA?,M]2URA]]LJ3C -:$O*XW9MY1A_JU:?!5K'TA<F /W$<&%.$:8T+
M@Y;56R28*@-\CN)\&NOS4[=.J3A77($;1;H?_)3%&"P<LQF7C4NV$_CEBVV1
M/<;14_-BNGN^%G%A L1H8A;N!0!YTFZ+78L(@7;ZATA+7*2= U-YWA5F1VSM
M,MH9=[^L@T)8MN^EK3Y*%5Q,RBF*=>;JJW^H7,XFP4>%88@_5;N.VMW:WGY]
MT-11==5$NZ[J7"JFC "(JFU%J\@H:%?WT+#-O?VBZNG5]$Q-S9B?Z"[T;1_0
MML5['S!IT99-JEZ 2V(T@]X4ICXZ[#@"Z#I[?<X";G4G3;=Y*8/-K_7=#5]I
MA3*^8E@UF(TR2N8:%6463H(6H$ES>X%!0]L5#(VA3()2R$ )T+99[$2JTBT)
M4ZWFTNV1J&QTXQ*X;\4/YKJ7,NHW5BR7\@O&^:<(DS+X"W3Z>D$DIIRK@J@9
M#<&"7X*]FJ5R7F$NI+Z3"U5>Z#LYNH[CUC Y58Y8)B3&1VF<.NH]@Q\,Y]5&
MY]XYPD,!,=B?YM8.AU(!Z7'3W*RE>GBGA;AX#&L/C7K*4<V7":?V4- [E[>F
ML-6"1@,?-7K*J-%@(\-&""X-/@P.+\_.-R-BU.Y]G!!,4L>#"(E57??I.!)J
M)(2"PE;&!!E42PB!ZP?_4B6B0O%B*(33:U0F=(7*01D-@\(+<V[="08,T48A
MT"6!_!KEJ_&F?:QS1XQ=QNK';03CX,+<9=+=!$? -5TG9_S04[-R"&-%_4+Q
MK[BZTM%Q_"K6=3)R85)5[S48D5+%,,"!EP&]VK/Z@FQ8B_BC"X&!)I-U6<6]
MJHP2/G7: &AM+9(M%L$NR*5SH] 2V@%SE?/6$-YH@GK.VG+CD0PQ;X=[.(?E
MG**,!P00P=QM.!Y-2MJ\#JJMTOL)!:=O?- /R[&S^1?H!;9"?]9N$D%0T!0@
M^[> <X$.5GTY0^$^(QCVL=C<O>IE':0IINPM7J[_TP;OZ-Z>[J3!N K9K-6W
MCCL/L3$?L3+Q!8%J2.@P-0+3DW'4#T[__&:Z-+I")ML]2"DD9';\0D:=%7XC
MX)6 ]8,+':3D2*@AT[VY';W2]=WWMYNFXOD=SZ3K7]U\&.Z\N]L1_LW"\->_
M'+QY>]"D3.H&&/#5CQ1EKF%3&_C=-H5K=0P#,RRZQK@UAV>_G1QM[1R Y@/]
M,853\M;CW0OA"Q9"RMW5%P^@SS@9M)#5^>9D,5O9RT5B3^4I0KQ1_WE!\X)V
MFZ#I@]:DT!N_W1% "A<4#NXLF7O!\H)URS&J;UBKR^I(_H<N^0G<BDEF%.5A
M"A.=6(+&ME=@7LX>>%)J?@8.&U2\/=++E)>IE<A4Q#1@?&@RI0BG[%%\'U,[
MKA#&XM68%[EO$3F,>4@-*=*)7!7FW^2X2VNR3>*9ES O8?=2:CE)E<LZBW%@
M2KZ2AK<7[3)0::.XT(]Z(?-"=G<A ]$I,"QOD@WHOKYDW.0,NN?%R8O3/<3)
M'H6MV8P4PH"S$!%8"0'3O'!YX;HY0E%/2LR1>$-EQ83OC/LKO()_Q+N^<[K]
M.J_#T^V%PV=]X="Q!*ZSVZZY%R^D#0[(N6*92)' :LE93&-$C*<*(N8^<4&/
MYD;'WLMP<O;BM8RY\JDN(<$*3^)I;"@".,N0$B=6ABK<W^Z_7E4=A@?,:7,2
M\48\DV.F5J5[VVL9:'?6LJR*C'FH9(8W84PD4/-W>WR1CSG.$AEQ-=W4*$!P
M -'-%$0#D\>%RY1D^U]=NO4T=HPA(4C[Z68?1W&>E3,7INU<U]%JQUFTA?VN
MQ8,R@TACMEZ$.3#5M\K&(HW_-)2N,P3R3M244T22>1]Q 8'\*A"5"FL1(VF!
M10/L;B.@$^&%5Q(I:S(\K'#,*E.IN(JS$D9S,3B_V#I4OVWM]F@\%#C <6 A
M"T0RR$QG_HC<2FB/D&@YT]Y?JRR)0']**IK!Z<\(+F:4QN_X;? +K^J9,QQ"
M9HA,<VY;V5=E03D7"$'5V\!".A?42,_F[C1IU6"'$1<48@&S6-.)(>@N$S@9
M0UE<(X[./-H+CDLT GD9-+<<RP#QZ&=TWU^K"8*/_DPO5)G9R!>%YMH^!"D$
MW9W&PO:P^=M#(JB]YHFAI/D\!W^GQ*(7FL&56(;R"FM-U[^4$JQ5@0HYS8MP
MH78^!3](&6NP)<;$>M5(&-)KAUTUDTJH(B0TBT"B3':RYH(F6 N#77E2*?&8
M&)_@7?. V-JGTB<6O?6)13ZQ:'V'[$E*K(Z@W$REGUP:-* ^27G7QE<:]<P;
MFA(X7%5]348)%]LALK3LRQ9>Y6_AMJ[*F6 @F?ADM(=CX-UY,$[4T.+W+%TT
M!G9F#%(S9^F6U42DBOLZ6^C$5<9PN%R)$$YN??!IM@]*"ITJR@*)R'"HDB:U
MKJ1?@NXMFKK?'9U#0\\$#MK<LE/)B$4X#U*;7@,O1YB^/@;^4:92IW(U=;NC
M^G62JD:"PY!R9%C\ XL5T0UDI68MX26GW62XB)0[,4M$B$.'79]J"*N[;+!/
MKSC#!&>#64EH7$1[E%=MZC(1)J=9I6/%9$YT^3G71_?<&=.-YQ/G ^AY-@*!
M]9/<N;23;V@VBECSW"-/Y6BN4Z8=T:J+%(RUFLQ>\X"T->M92$C:B+\*"80(
MJFG@3GA,)L&XC"-*$M8"]WO=)*]#I4 &&EN CG$V'FR7'2)!8Y77L5I=K6=P
M>5<]H1,::%"Z@M8R? ;B?7*<1N17:QJFI$0F\QSF33 @>*)R)LBWLUDQBE"*
M0VT#M.2,+!B#5N3@L2T.O6 B-YKO3%N51<S50O2L9%"A%8LDPMB]$ NWU8?J
MNA1LL^KAD;!>'O]\<7QT0J/Y??"OCR>_G0_ZP<"F>6.ZX4^Q EU([[%4<LQA
M1XGUL,%B\/4K=K&I)HL++CZ?G)X/_CUH$O];?E_\H4:K@]3S<*!11C?G$AM+
MP*B@X16":5ZP @32U#!#;VI? JU2*V9-<A &BH&0AC#U"U*)<XDX7JI_ 9H-
M0_)55PF9@V8I]M_Q9?E]E"JC56L.FP5,5=[#L%(3,<M9K^>8^P("4_E1ELZF
M[O/9%+MJC1:!Y8ZS:?9EK4J"?H!'2?#T98A*PWE*91>ZYVLC'1OB\,C3S2<2
MZV5LX2[ S=-SSYEJ]EUOR1@%IK@+\J[.JCQ03H_2O\DG91&IZ]1QDQ><K(EE
M57*KNBPND,XRX'_H);)!4V90:/.7G;I'<4733"Y@55;1^FUV6'4 4$8)8-@_
M6Y_&J 6FBM4RJ,E[9[.$&);BU!P@YX92KV@PDM$17Q-A[72QC51KS&R]5HU6
M#R!5E0:_(BN?I'I5F,M1HS]#^P5YR4)IJZI5X:.6S#M]1M;[5'6]!T\;:K3:
M)@AB37KMCA/7#NMKPO#A^,QEYY)=?[<U(:LI-,$X4X.N'A%R9/:FI7IO$O=J
ML3ZF^=3MWQ"\XTP"?5PZ-HAY5"<-^#2!9W%[\!@)?*]^K,Y[*\$8S80/0$MJ
M;DCZP#$Z&/!(!S2F\JHDH>- "WK3?Z* VETLL9=XC_IZOT/"JKHKIC6_H"4(
MH<MG4!BS %]096AQ<AC!T"\ZHHJV)IJUNL:"M18_4W&Z/>@UV,ZL4B7XE>@O
MPK%DJ9SP$@*S!VV9$5;Z^&FNB#%L"@J[D-+1[\[;V:[/RZF,;K^>>WXR[Q7T
M?3K(3K!QOZPU1R:C+96-M: 1IZ)@"0WOFBZ3 K+VG\K.MYZYQ.":4>)3)#@Q
M==TH.H*V&?R G7QRSTRYQI>HI;W$/LRD:%@2UA;66:_$PD=9]F/!'!_D9Q9T
MA35"&J20;Q9UX (>HXKM=%';#!50$,$C9KR WD= J^ 4:3T33Z<X<";'6%:!
M6'ID,4%0@3W7<R=B@"9NAOF,55$N]U8>Y5J+/;EQ53D<2W)3*_8)I@FZEZ,R
M2U0YIAAZ+>3B-%P%/5:)\EE3G6$=WC68-X/)N,G/YBN5Y9[V79R,1H@9EL$!
M/N EQJFZPK@G+F*J2EW=6Q1-ZQ$;-];B+V?G)_\^.R6K<4Z1?3J=2<R(&/N&
M6$W'(AV7[9?\:+$2;"4B0BDE;-S-7.!A65M3*JUB'M777Z'Y-3Q:8J1Y.*\P
M&$[MN=Z2$#TRD@X;!: ,?VYF2D'U,)#-(2<M W0"M:)L<%-Q5&VA:"T202%-
MEL8".<A-?2N@2_3V:D6:ZT&N5(X-]9\N!4"LZ%0N$!IK0$($(;ER=E.J.FLJ
MRS0)'P_'5GM; L18"%X[KZ[Q47"E=XM&<B[8]!-\ZYB4+?0H7917O9*+8F.&
M1LHC@V4CTC*B[C'BZ@9(Y[(>)+55OC3DS%[VW2% VH(YPH]Q&;%9>[&P[%(*
MZ==LR+T!;L,K(%V!$O43HXZ8CZQ1BY#H;S":2$ZR+M>(P_R28K4>$M@$N:8+
MS72L3T:555C#M'G[L1#L1)B<XR?,<W# <Q,]UXO#BF#.4X5LC]*IY<U12S.[
M+):T*DLKK36!==>2*V'7;XLI8+5D@JG64Z,P]8N$'KWST",//7I2E/?"=;D^
M=3X9&&['8-_F-LC<RE1G!JLW2]*9+J"++;*XIK6H-:I02P6'79NE<@V(1)_3
M=EE?@AW"Q@FCBT:&6+9,35@(&H,_XWSBI%W:/-\>0R]ZQMY@ZX;NT$&K#PT/
M)D&:>+U,V5&^&B4IX:*C O$$7,!7\](YH G-O&&G038AUM>2[#L.:MF0EF6+
MJ3'$U![MFBVR3KFHS-;J3I )*)8(#%($9@(+\C*5@%N<H98;?L-:$1A#4Z#5
MA)2VM5M<8UC&B:6.I=XQ0)S1/BX\O5GGR+&W08HD6N/6OHD)AA]?8<?^4R+&
MBRLHPEK'44F&B$,RA+X"!8;XI7! 1'G/%O:S-!Z$;R><C-*_Y#Z;='CK8_-F
M<,AC3)%I 6]58[ O)[K4-FPA? I)D%L:+*28$K2-UI@0<:G4"P'/RZUR!J(3
M&^Y)7=T(;]J1U,]N0K+7XUL01^3@<J6IDJ S-JA![H&(=="-EAB%B3\#NQ'D
M%/Y,=.UL=]2TMNRH.)EL*Q"OIBC4]!-IK#NK*E<WDK:R,\O5W/7L+DRJ 954
M22;:[N1\&]9$L#VMF+5HI;IS%Y->#B=*Y?IVU-0!:>A(,%$0 U'F;?KA3BK3
MT<C(*BV&RJ:09+29".8!+HC0I=;1[F?AXMB^V1P9F?TXR[-FG7K$IO*,8KW-
MI,+ACK2'(=,Q[HF;AZ?)F]N/?6><%!G*%"&"].S;4H)5.K<)#R3@3^BZVGK6
M75G3=,V5IJ6J/LFWUN!\!/M"%_S1PAXIR=5K>#V6;YD*^]<&,:RX5JL90,P.
MGQ!<<<XI/E^57;N)MHVD2 .LJV3[9&[79Y499JLYI(^AXR@>]9D@4L^RF"BN
MX3NR81A2.PSEXN@/*>U((CJ=$ZMHJ;3ZU+5WBWFONK'C,%>%1YN).25NT6HN
M[&VT%'1KZ-[GR!W<(\C9EM7!:+F-I DRPWABHIVED5U/='K2AZ.!CB93Y7-7
M[_,X:6/:,;=@)2U$M^K<2+6<-:"'%8>YC4["ZNG$6]P8&QK\X" 6#KKS0YEA
M$!U1G#U3.*(6#S9MWG"(."62.FL;UO&]Q+=3T2GKR./R1$6<A!PK%B_LWRKH
M:(Z:YK,AQK$+MM$KVNCZE8)EQ&]*:56_69/5AI*K]*888<K&<I$CB,(YZ9(C
M:MD@1*$G :N)4= +IXF0EJ9FLKE&1*3Y<.X,0(>:%OINB9PSRDFL!F"*!"SV
MG:N\Z@?LO:**4U/9&0\RL"01SJ\[_85/DL=2R2: SNH@O8H9^'=BV8,Y4&W9
MN>NMF<'K>@ZI*65-H7+29!3KYGUJ'2V5U8_*QI6) TXW-=/U%8F%=)NFZ#>Z
M#Y$Q1>UM&!W79@A--*Z):R*:# =&Z:)FIW1M=W,Y!\,![UBI8#^AV+1LDE4*
M"1]'.M'7Y:;6G "-; "/!_5WXTL[2,IQQDB@/,3<9BO1Y,)K@X$="X\%\N)T
M<P=M"-+"RR(Y!<G19 I&[=OX@X,LML:T,9,D1G1$R+FB: (7+4>>OE6.W:JJ
M5.>SP"H_7!N:B8"Y" 0YEUZ0O2#?TD&R16L!0)>RJ9(_"O+JP!>;U4Z%5_BG
MF,4>0^G%[;8.5DI0._BA+1D2J9QS#\?01MI"TNHQD%[ [F#GQ=,A1D#I8+;9
MU'6T87OL:E/ AC^9; UVE175T5L,,ML$\[R*VMF_T'8@NASZB.(*&E*R$/-#
M6T8S6-C0AXG99AC*(P?<B8;I6JGX6^W.=<VOK?G]QCO55SN4MADK&$TP3)3B
MY$1,LG53Q7I4J=(>@*Z33]P3Q80 @>"TGA]_NL!%&F=B6F$#3? ?'I=)[7$"
ML05#]15I1T1&-WB,R\S4=*C">8$\')I(:9RHJ<S*1*5R-L'09]X/D&AL*OBN
M!:U!UQRE-V@WWLW9CW.2BSS.1&INHYA_;)"D\T1,VXLCP[=8?1;&:9^N9C%.
MB1\B55C\7:?'.\GZLTQN4="4-B3%[S!]7L5XF1D[UP,:,%6?$207@4YCR5N[
M"#=,?).'8'$)<#9,:,+,UO&OU6@XSIQID:@$@6[%B&\*"1,,Y(O;=/-5-!JO
MB9\T)!(.&+-@SC.^]:-0D0VY:WQN+FNW<BW141,<K5_JZEM-E_+ "( S>C>H
MTH+O5NWY[;5R))SJ?H=M5*&DS:7"\I3L%N3A+0B+I?5X6D;-E[(>-7?@47,>
M-;?&"^&6BQV$9RPI:]1[U%MBO#= 75(ID!I@C6^&NV;*G)4V[D-WE1JG@(/+
MRC'=9!"EE3D932%6NG?H\;UX"4:$*BV)%)$KU(I*$UH%63QF-3- ([],9E ^
MDQ:3,(Q5X[>C.)NB>:+92.R#T 'N<^2L"$.LP*:01.4FPTD*6WP\9_/&'2]=
M(>(=ZL+S#8L47N0O"+SCN#PR@7>HD0NV\25BO  ])/(0,7G72%RI#!9B7K_6
M=S(L6R[WO>!YP;LWDX(8>97E)><!'20]5>50M(@06.=>BKP4W2Y%%6(3?;<R
M;Y.F30FP,S6GC9]>2==1K-@TO]R \_]V=U0-<Y6@_XN43BK=<KK3-1_TT%0(
M:' >"")NSO(R-HYDY<K%C$IT_#7^034A,J8/., 8PQ_7*>,8ZUD '#LV;FH]
MT\)Q%'L52I?+<4^E*>O 0$=LWFGX2IK@,1AEB @M^IC19R/J%'BLPKDZG4(L
M$+(2UXLA>F&>C:G>) L CYX;_^Q9H&<BYA;,>@U=;DG#OVOBP5T%M&L2]LF!
M@;K>/T75G3@OS,@8UQCK!IG<CAX+G<7A3,HIW5/8?#+44Y3DT4AQ<:#,CCJH
M7EM%AYS7.LEQ5<,LM!069W2.K#+-):?L5#VK^ HKLC:B*J['4PS$AU#77.P4
MVT%\?.5A+,+C3?$4I?E*33,Z]K.0H5/[43\8A*$BX+0)QMT0BZDZM:P;=*-A
M>R!%EL3&DN4%Z9@8.FF"F.&/JU!?%)S$8:RJ@)43Z7*B7,QN;95]T)9^0(NA
M%6N5AV<Q]4QJKY=N+) H4.NI*M[%27CF4_<)30OH]F$6SV321$7[B)FW^Y:'
MGE,X/*<IHN;Q]DW"T7>EKF3(=Y=Q'L4SO#HV<7PZI\VQXWU3+UTW=_!S!4@H
M!+83Q1H%:_\UE>.DG.*5<DW&7(/&< $Y7SO$IUX*O13>Y;;<;6SA4O.NK;_Z
M\;>RR#1,ALLY@Z?!DMPBIJX4ZTMY1W)7VJ_WM4M_OQO\;EB6[7E^MC7X?':X
MUPL2A9@@9.[J!?(*?*T0G)=A+_CIY.S=P1:L:D^7OIJ&8!J0BEX0<0N^(8<E
MD7\*KY2]&-Y!##_]_.Y@NTVBP(41H9<B+T5WD:(LGJH0])A*>DA@" H-3F<,
M^V!$)A[J&F=R(C 5N$W:"C5B,])G)GAYN[6#'T4J(IG@,;DU2N:J%QSN()69
MS# K/TXG\1##:+U@*#-59"+!&HY+?H0QS[ L1"H)MS46F8A@W>@$_N=O1^]V
M]_GX/;W\.-C:W=[>;1/?2*5Q!,+M5";J_-7,2NU>F]<?IW]H2MH1W3 @4'TB
M,:"'%UGD=SIP-!-/)X:ND"GD=/)$A6A7H^#BT\ !6X^05BB@9$TQ0T(B'23%
MQ,W7VVY=Y0O$T8V8&Z%7D0^,1*CS\,P=!),T+8G"](B_*S79>7,+>.?\#%'O
MALT.B$WA2U,"V6+A[3>[VTO'2S<8UTB&@:5 3 @(93%0616T7CY?MW9N4(Y!
MO+@7+?W3U5-V^@^G<YC!N2"R&/G.-'LPLTF8H*PN2]B JAMZC:BV0ISO@05'
MF4!9\\2-JCYHCJ?VZN^+";W:4^M:8+R>7E'%O&TD>CDND\/3U:6<25":J1G>
M&1@"])LN2VD2:ZJMS)DX#*G--4]</"-Z,,/256?Z720'R>L\V'3;BP4E\:Z[
MXNL>40:402O3=>TBGWJ^\+JN,7.=-5)]<<1#Z?(N.S<X;C;("(:JKNG^BO:K
M2+HFF1\6>DBJV YW"3M320P]4RP"R,5SX6\P!;'HTE6-94A/#,U&G56H*M H
M>R[31!K5"/Z(AZ)*Y_D,.EUIUB>=@A<N-*^)J)CSO5HXZO70I2RKB)'B%*1Q
M6B,GT#K%7E5;E4OI2Y3<]'L[9Q.BY/EVCQHROT<S,YZZI5'IAA\C7H8GZ0&4
MB=\*I7CQ23W[VSZIQR?UK),SRH 06ECZABJRM<(I<5"S]E'J(%=5;!)%UY(-
MT1(W>LH:XB;K<S&ODY1#RN85WB=AZN[,4;$+VAA+Y5QI[FE_$>X]^[MTT'%1
M["%E3U660V3[0Y#&M^1V^Y"F%\1;=.\#J Q\\-)+UL-47)T#XR;ZA<</+A[T
M5V*\?%[B6'&0A@T'XEZ!L9H8EA.IBJRO%A//.)B^Q)-IO;"ZBT5U!QJ(S:K6
MGB%ND"F5SM.>UG6NJ2$JMQ.:I+!P16>K[1M"S(Y&6WP$E;G4*;Y5R0:*P,3H
MQY<I47N9,JH95B)BPFL]Y%H[9D:<"(%KM"6QYH-8831@12M<0_@2J[19DY[+
M+RW:;-?*5N6 4QKI*)^-+&C'6F;D;&MRJQFR7-O?+,)[+?]%C6#&C3[!3!>Q
MYB)'P!-'$1!J3/&(Q=I_(59V""MX/./#TXI/N@I'F'ZU,Z!8\G2W\(%A^!!Z
M:#5(KR8PY)J!&(3#BFM4D((B?(;=T+Z*YJS%_@'-("/-H/OA\***I!?B"WYL
MH>J&-)ACL0ZR&?M6#=1,MV&"SQ%?QD2R<[OTO>#XL"*.OE4$<&ZC3%PO(Q+E
M:A*NJ)A"7F[A#)4ZB0$Y1_7+?"'PHHF9:=_9I><(<UTV8-)'93**DU4&XU:U
M_2SE R5L!#$V#Z\#]1%5I=(H M%._8S+9]CI:0:I:$,\<L)M.EX. H3EVL*0
M6.Z'.0BP3KQPUU.+OVGE6FJ.B2IXERTNA4M182*$3J/U0M7MO.<U?@7,!$['
M.:)J<MG6/=X11+@<\AZTHF<QW;:&HID74WW%;M>*3[ZIA"C>5K93^S@% ^IQ
MRZPQYVKD.N!TU/P/(MNI9%\]4+C>S)35Q7H6*V;ID@FZ?E]+9I*^AS+6@GMM
M85*"%K)VS!1T+9AN*D%1U)(L'KH>JZ=-B2S#!:]XO?0,.'6;F@.7U8@QY%QK
M'K9&WIC7ZH:N4#XPX[V6I1T<E?INH+;K;(2/-J7/2/#2=$>>!2F_L*<VU"4<
M%L[IADCYT(H7J]O%:OF=:,,.Z#PZZW?C*R9S[=A49[_>-(X1>NO^<<H>MMFN
MD2A$X_>.V:XK1]\^MYCTJ_EM>[H($/J'ICX/A6VFB,XROI8V8&L9Q(49*9PT
MJI"VEG;-<"%7U=B#X$+D[*I1I2AK&U6#>=",N3/02"N5;MOD[7!?[%6%+JYH
M762G,E>M+KAV0EO83+MFL)[=:),;*(.MKHU3>066)7+6<D6AW +)L#845@F,
M4Y3'16,?@4X848,>N>N<@Q;):S0']46I>SQ8(;4J$TZ%I>#,06P2>1F.**!I
M0SX9"J5IP*[DHE>AUPS3E67$N(Q$S#=UQ33NSI9<-$&5:K_?XE@Y*V29AMTB
MZW=0'#U;SU87WK(%<FT507=K=@WS=1??=8"4S?\&W1@*Z\#^H< MNYL;Z^2K
M=4W,'N;)NO-QHSOKCCSX%7JNX:Y89=02&]?5AZDUW0M.5*I37=WWD:2%:JO^
MTJVE[UVH/+;0F,5@(-$,FUN+1:T;+2*&66D*3PU8[@7R*['!4Q5%S5CP$4:5
M!@-H**:B>A6Z^3.HUXS?L]54A$NZ7^TT$]*"HT=AU3Q):[:U*'UV.EL7CO%[
M'*WB4JZF)F0C=-_6M@G-NZ]($L.;RI<K^HE@ENA<SV$9$87,P"V8S=P@EN3<
MH0[1F,.V@54RF5.PA#@>W&:,X4+(\KM:+^X$W63"])RJRUCPMRPH<*M%FF3M
MQ(CWS;TG<:DM>-XHB!DTB_NYOS8GP53*HE$K&@RG/]ANR2TXL*:2F^T,K>KV
M6,$=CQ7T6,%UG<*URU@1_(-,BXM"2KI/.*1+,?@7N2O_N#CLH8*C<^(_)17%
M19G-)_',WIDUSCFVCHU%CSE3IDFNF ;6M3Y'B=3(W%+6>-AJ=QR]%D.GNKL'
M!9XHC8UOAAF7G<S#>3 M"QR./4](A:+><SMLW-*,BDV4J4CC*976L*<0=07O
M)0N\/,,3!-X3%^C)(#,W632V\J&]Q^SIM =^2FM#$$F9Z<M>["G,/0T"#XVD
MM*ZL^<IZS%.=+],<D>E;=7;H%_9,>-]A.JO7PS#FSH(ONRKC\G%,ZT889*%L
MO+FCH\+!-1"JW A"MI7FX;4;XT9X<@-A:$QA71S:)@WSACA#Q>1-^=LB'XB]
MZ30:S+(XH01"\CD:WF$=*%[W,"[4,%XNE4U?[!!S@86_<O(B>:M('LF0[!Q*
M>5VM5-9T)8CH<8FP/W]KY27S;LK2I&+OO".Y'(-OC^'/SY>'7-?X:YB4!%);
M$EM:)H>UX!$;Z#JL= BF_' H:Q&EC;T;H\V)HZ,)4XUJ;?>S#YD_%HVH!&]H
M:C$@3CJWESMI1&:^#5KC[TTF/%&O$@RNOE11:\VT(5GKT,4K78B.1@2_P '9
ML/H-H?1;RL\U4NS)/V#6Z#C/2@9IAZ+,.5G^;L7BEL3J [<<8@L2EL.0?&SW
MM*+L-035"7^VR&D=T:NK&DZ1,UB7\D971LN "<F;&S?*62,G#OZTQ,8N ID@
MX1;_BN!M!H=W"BZ'=SM5UYA'MP*0.Y=;$RF28A+B#Q#Q_JR=GX=.BKM11C(B
M-F*Z\BXH+)X6\=:7./R"03+]^Y%(B(J <K3YHP)4=HYUO=-PKC^B<(#(2>I-
MNQ=EFD\P;6B@<9VZ,[6L<C"=KVP5>PD[$3UX;E,'S.M#T[A0]][TKW_9>;/]
M?@'-?@IJS#&!K"5]A&0GEC[D%^X2OOX7(M*^D-E5C!'N.,_Q<E#0UDF"K$PP
M 2H"\3 I$PO314AUO"T=(K$U*H=/5!<7AO 9WAD<46@?-R830,<FMZ)!"(W4
M=R/DC0#-,<8:P\&QUL/$3Y'C-3T%X%5=#&K< UJIB=DL@4;1[FK(PD)*2)Q>
MJ:1.C1Y@I7=4TY3P,5-Y'G/M=GAYQ6> 0J1#0^AFZTLG?;5A.VJ1 #.L54IS
M7-VE+W8<9L_PGX!PEE1TV.TM*DY!95.O=<]U9H(9[B@3)6>OB2$R\EB$_BWS
MT \^2UAQ&X2[BI5]Y^@^\XFC,Q<\;J)+&%_%22\(,[Q7T1O0+7:+501,#WI!
M)*;(_T,XZK'*QOJ^;Z01T%/80;E*^4-M//%%:AWC[;!/( I 1F[W3=&":B-;
MP<7.\3_B2"<"N="2&8@ED[4[96LIN(E'$UEP;!F0_U'=F&8S11 =^$".:=,[
M<3^P/F!J,.!7??C_VOO2)K>1),N_@JWM':MJ0V9GIJ0ZNG;:+"6EJC6MJW5,
MS<R7-9 $DRB1 !L@,L7^]1O/CP@/ &2F2D=175@;VU9))!B(\/#P<'_^'B'P
M&[+/;+DD$(FLB.I<+(NH;:J18R"FYS>+B>6A.EC !;CW:3D3"]?I]B1FG19F
M01P_U;R0UQ/3S+DA]Z,P['R"L_-Q)&#N-\" A)@V)P ?A-I<-D.Z?(.(#ISU
MEVP([L/,7P(-<-H<GU++)%3@V*7LJ+@=P-GN3 Q5(Q>^KJ#,,(UX#(1\/PT\
M3E1Y5/\<C,EO6'I;P5F0]K([.]JUBB9S\R3GNJG:;!8H%K*7YHZ>9#UU$)(V
MISS#MTG9E-/UHA)<$<XB*0U@Z$*^-,2YU#,)CQ<H(K_;M&MX#H[!J;8]025%
M/)=W/OINJ1BN,6:));S<2NRXX*OX]'370/%PL.N:HF(7<FSR$(TTW*\32C+.
MRV:EBEY P45F>)9/B\;[#ED@6A@/+Z06.W?V5>[Z@(.KG&7U3,KE,[2.74&9
MQYE6F"'J)V11K0;73W8V[F.L*HD36.C8*#YP/LMYTC*34C4)-M1Y-MO:MEK;
MO 0MP9S*+/X#@!1(WY<WGZ+I-#6R6V3G;JTJ=@(K\O&BI@WA=C!J5 -"1X#[
MH;65?O[B*J<KH\H=&C]#IWTC)XTXH7@ _,/TYAM<G#!@NI ./&U=N=-:M6:'
M'B/%JP)Q(_XZD,?QKNRHEWPDQ6#0\@VP\HEWQEKKF,.#L+?T AJN<QZ2L9MW
MJ=/1M:/%D<IF*V?<FUI+FC"](Y]@H-BMXB)CUV,!_$:MD=M=_@8,+?)+;#(2
M,00F-/=FSA780$DP*-5<]C(' NA;)*_IY\!*U_C9>-T_Y'@VKFA3E8"@\&QU
M7R9K.F_N;$ MT;[='L\;[8JP+RE\IS^U4M KB.$C(1U99\3.3N#*P!17^*B'
MTQ[*8>,^REO"#;I,B)C+.0*^T-"3F,EFY+(R^)2S$9\RXE,^'Y=5U_$09T#4
M'(YTI,2*A%.)[M(1:B'M,F$*9RB=1TE3K1<%GD*$LBOW(]6LX:B0<KG4-VOB
M+KW.VRM1E*PLJZ1U_K>J5WQTWAAB5I'ZWCLWF$::E'<<!,XR*I ;WOJA@(*"
M/!-)Z4@]C<Y,>C+=7/"'#JD!WNO<AQU(L%(VBKABUVZ_\&&O!+"G(C\02\-Q
MQFE&SW(.P<XF.##H$.(XEJX <5:DG/EP4^/,5,!##!MO.BP80170Q^&=Y) S
M5F>\]58FDP/L2>[BJ5]:3)G\[ .W!.XT;*3]98%+<WDI( A).&><'58@YL!,
M1=2\>4A"N8MRSI;J_K2D8.;6S]1L4EN20TL6U;4>P>Y.4UP&@)29:K*:E;.*
M#+,H5R0S4T.KK+&8)IX.[=;XB)MXJ,J %O?\*H]X?\/M)]X>8E6H4?(\+(NW
M^;)+K1*XA:/^?#+2+K( F*]2;A6&ZH,]17 .*(.$JU=W2<@0^=+ ^\H3(%,0
M'&64>HFXJ#-ETS%LU<V3WZ=AQ_9=E @F*5^VS"^+9AF,*'^73UM*JM$YW!"W
MZ&5),?$PGP*-V_G<NKWDP*Q)OLZ/+]T$3+9Z<\7<AP]X:+D0I49IWR:Y3P-Y
MF&INJFK"-Y@[&K]!N:@H5NQ@PC59C"LOWMP-P;XL'(F[,LJ(=/D;@70C:G8?
M(@^M@V^^2?WGHMO(X.MV?VN=BU=T:U+3.3$I*I^X(QF7$C4N_BF;&VH6N/N7
MGGJ(^,:H]T.*OP0Q]%>W[H2Z^33V+?011,$T$9QZ&$B#EU@OM@T\H\Y@%MB/
M*@JA >0_._G1'2%'SJ:/J&9(?W?ZHX64T7>1]+<JOR&;[7Z)3"*B ?DFE7M\
MU6Z.JOG1NIJZG<4?I-.83CN?@ DS/W71/EZG6T+@XH![FWK;>:8<%%LA>LGQ
MVYR(@A1 TM"5 N>,F[NRNO(K*71-[LD$YY3M[?<J$3M=^82Q&2+?/(1N9]U.
MEI+YTB//+4I.9RO[&&Q>M[;_#%S'<#)V!.!<A[F2-1$%$'8"RUZA'$S%!V1/
M/ 5\\XV[G D1.-6PZ X5O$#P3%'<)(=_UU?8+(#-Y!N7X:ODPR*>$"DV0JOJ
MIZWU\_XT!$ZQ=Y_R%;P@&AB:D);^V&59T0-7?XEG2"KU>KFGY)$PV6M[:U2^
M4^]-ED*Q8(-,$2HK^'GSWN[C[C"E3-$*+B'KYBU\T5IZ5Y9OH>/L(H^&6*%?
MW^[F',=^6B"*;M%H\-#[N!NP2#[[ XW%&/J'F9XM'S<ZYRK"LII*TJ0P20BI
MQ<)9[P<:)%6D 3R$6=#<;-$%.E>\T<(O[DM+$'X:R(TEG3S2K.,S']'<=X 4
M>($AA 15:3E//"PQO:Y *EYDMKM2\1U>_=OK$MNLOV=8Y\++ 5970N=WU$(=
M)0#)8* .,A5\769@R5M. ^WZ;K:10X(U$8!*UH39 EGX)#Z)"C&!22N&;89'
MOC9:;9Y6MZ6VQW\\L-#X]=YFVB&.+],&K0G/:HW.M7_FXA.104R6F+6CQKEH
M"U;J<%*YHY?W&"DP>T7Y3!+Z8-=-)LZMT=H&]DKK6FP,0)E90+@\J'_@0WP1
M=-'6DD%)%"#(373*KR#Q9A!#L2GHWC\&JKOS<CL,@Y+M#Q'[*JX*WFIJ(M15
MN66OVWFVO)&S5KH;]CS*7I>(#[CPO**+C@LJ78!RC?O R]:% HSQ>_,61V6N
MNO>4'T]B8?NNKS&Z"7$K$>N%T$3N[E3VDM<FPF;[VO YJEVG M92B7<R2FIV
MC50]ND_OS_84C)AQ6N-:+D=T*:"S^=W:%QZB!Q3EO,Y<W-"R<Q$3<Z<W??9Z
M46%SN?7'+<1+>;-?\Y2'H;42ARW?ICB]T_ /-YQ&VD1KT.G(\1V7\?AZL('A
MALRX(G-@OBJ6L=&UT4J-.=8[9(-Q_!C.8-D8"^P"8B[)"&N)*PY'IHR@M*X/
MJD^H&;J7K<IVNLS=U7*&?R"O9;<".3[MRF^V[F* O6;1)UR"#5HGFF>BZT#2
MK-#,75)BG4DS@8?)!>ZD,:FS6V2#T7)7A$W$G)>,7903[3HGL:Q]9Z#DY!"5
M\M0TN?G5J,';7@F+6EXV(&'$+7E3='_]"ZLFX0'R!CNVHMN!)ELC2B^!^4'N
M2 ,6[OX>VT>"07. 2Y;!NQQ)S>X13T$0+)F!O1%#QF$_Q<&)"Y/+#9]D06%%
M"[3A;9%+#AM=C?'@MMJRJ=+XV+2'$%3M:&FR&9FL-"(^>F@X3GYZ^B*ZVI%Q
M2=(B!L/YZT /C2NDS(H#&V!ZI<#!4S!S@."&K#%%47)S)0$@&<" E4_C=5>7
M[J/'.%[H@.>(65/*B5TX%-XZM;BJ#DDMXQR>Q4 J]N9Q;EJZ+;%W$*-O&!F]
MEAKM()WM#3BA@<]^!.A0;4!=L@Z>Q@\^D:EB(]9=\D>_(HH858<^9J7VSEBI
M'2NU']_L!N_O+XOF;9.\#+D0[/B'G<C_97#NYT8+#KOXJ>[B@\Q+[**?WLU#
M.8#>Z^!]=_''#7N[@4%(-H(:E-QLKS2R-Z>IEIX.+/3XV:=2+MN,>M:D6#=(
M.*YX5<49@64,O0%4D%)8$69'/^@U'N(@5 ZG;L5^ (V_?S&B&-*(I)JUE7DG
MW#UE6/V_&(D*)@\JAX4/&5Z&2M.1YY4')GUC6.<1F2(?T-4S&$"?">V_3)G[
M-(,1B,JB-^$30A7@>UL"#-CWI&B &[AVVC*PN;=YN0C(-A!I00FB&UYZ+<BL
MMO&BAIF=[/D!&GY_3F(YQW"Q&.2:I$LHS (U:J3-4D _.9^9]IW.<+>)?;*J
MG?#EK]KH4G=L@DH)03!AR&%UFO;>?SL(H8D*@)0*0XP'N]7Z?KCV=CTC)0TX
MWZ+H/XJW_9Z815H8=;0GAA.BMX]+>WZ_&U"3C^8WZ4TZ#4O4IX.ZGOHVA7F:
M"?3R =+;R-MUGU:);"-"Q<L%!-F380)!*BWZY$6W+<ST'V,9Q#&HO V)\8+Z
MIH)F]Y(+HEXC03:WD6M%+9)N[W* >3EP:U7ATH@'S'(F!%5A:;.JZ)G*Z](+
M7!2Y. _[-+H1>C9;$ZW(31)%80H(M#K_;BW2T-Q5QAFFNKA<;MV/H=>#ZM-:
MQ=5"-'NS!Z\"79R9*MP4?^9YD08Z;G+MO;IIPCO]_M \V^NP<=4'>Q^]1\6E
M4$P:3#'5=">X4<OM#KU@<46>E<YNSI%=9B1,V$?SO8@,CQI/BH9 *4&EB>OT
ME/%3!(-WAY&_$-<[<LB,AK=_@,/Z0SBGVU*3T%' 7LE!)OI8YBR.7.P.?\HW
MJ> O7?@W<%]2:L\0@8V&/!KRK_"@%+Y.B7^X(PR D$:O=W+I0\1C/F?2^&2U
M%+C/<NW8\9\+N$"JML&^ZYROC(J3NN8J!6/7J%.0T/8"+?>X&=P#"/]N>CH9
MZS2:_VC^']F/*UN#NN)0.;,MKNS,PXU"KAS$'"J7F9JRJP9QH*'Q:+2CT7Z4
MJ)?P1NLZ#[%N\.'NK[W!5F, /-K@1['!>0&DG9SUVIO 4/9AS >RAR%>H(!X
M%_P/= L6UA'YVZ@.3=B7P;)Z50LS 9)DO$4\T$ 5;LUX9@Q>B9#E=5P.Z^'R
M1J+'<??</,"-ERU')*R-/%4,L5&+M+N,D6D% "90_+AL"Q9#=^8XH&X\$YCD
M4#H4&R$&KPAW&/+\V&DE74<ALT+E@2BMBG,$#9N^$9^NGO)"7PIYY*.L6 KJ
M4^M?NR2GAWW)O/^ 7H7DUAB>B*Y1I:34@39YYR$*Z%6<D7[!>L("C3@*[.LD
M_J6?Q2".]8FF24'Z1SM052\?YUD>.:!@:#61^!Q:)\+/^1!(4&GDN$>G7H.F
M4]#-V!@[5GX0@]1SNQ^9SS!1V,\';)J[)\???R0RI]#RVGH9IN<\@0\Q@=09
MK;DM/G%Y1G.;Q(+QE='$%W.IW2-T)1(V'+- B,-,J=&_: C!RDTC2M3)&3#B
M;+RFX;@'GIV<I.[ HV3853%K46FU?;W/=RRX52Z[RK>44,MF5\Y%4F]7R3A!
M[M#DY'+K8<%*#&1$RZ\*-[4$$_'NGJ.?-)FT&T*%9Z6G%0N<+=H.F%OVR.Q=
M& K7SENW3$=S1/U9<<7=\Z$A?5DY?Q[E%$T#J;25"ML5%FKAOJ)TP[NV \#T
M1G1#D=*^WS!BR^*;"-KI-HMM#5]XA,6G^"E;;9=5,:N:PHP ;W3Q])QS1K<8
MBOK.6PSC_/7KEU='+YZE^)XOP=WBBX\>O)+..&>*%0J3MWWSOS[LX%+P>7Z]
M6TWT>XWRQ9/ &N5-#1TX$Z: 8I2!WWN2FFNX@=QOSUE_4WJ2WV5%^RX,UQI3
M$>6R\9*^CMN$.BZ*W2Z8IA>R+PN^"46^4U7?(( *VT7F(E=BO R!A^"WMWK
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M/]IB^A8862BV)?.B;C:F7WIV:+%;?&F.KO!^$=YCLH$/X;G6.J+HA3%*1W4
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MP;UB6K=%9']H1.6TO44O^VN6D6_?.8[KJGZ[*W0=L'@U=>)T4W'Y7;\_ ':
M='$F90CX&NHIU=J49$X'GDN$(BZ^$\'+CBP1!N/N>DN@%;(Z#S)%:=*6!6Y6
MH=>YK,HC9K((<Q++0D<73Y6OU^9:(5'I-HUC\J+-KE4_\>_OO79?7M"XR=[E
MS8%Y^(ZX=BLT:R7ZIB,.%=A-O44,(FD-A:G0/=2]&NT%JL8TRLLKPO"'YI3?
ME%J2E+33,GDI5=X'%1/"G?[P_;<$?<I6<-PS?][A TRNS=HS<L(''J4,,1:1
MJ\]RA6MBR_9G5(C'GSU_TJ0TN[!T"O+(!V?*(I"](^> L.\X"6/GD2C> HOC
M?N::HM*6GTIN<CYOI =>NL;U><RZHQK:\ .;0I!\]&5B@6CXPNS\38'F\]?$
M\;.BHAE=4'$FD &T)7TVM@/3<.[^?NH.[V)S<$=TF%&E^J-+]3R?$7N3T![A
M!9;9=1K_(TT4KSU70*/5@BMW[HUPXZQA]C"?<KC)A VGWWD&:UE^74*\XMQY
MT W!T=QDBG S691L5XYZ%@,C>M]QG)U@066WPFJ^/^&4'9_5L<7HB8RT(KL
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M!MW6%,2]10-#J1C_G&\TFZIS\5!8\@<O[G'R[/S5P_._^PJ;MYJJ[L!^_<G
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M/YQP>O?"(&(.,#N8E-0-UW1.33.D,CEYJ*/P4^/'*J&C-T0S9 CYK=J5G&>
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M2#>%R,N19O%Q\EKK?'PTM.5U4?J4[\Z?&B)Q)0=JR2K6V9875[)55,?/:V5
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MF>@[0KNX!YY^9PZT<+WHO0TQ'',0W=BS;_?)U:ZQ(4Y/3*@AS]]Q*,JQU,F
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MX*[A6)U=EW5P400M#A"L$S.F?10:!^,/:Q43RCVQ9?2X:4RV8J,V:F):2EQ
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MG'U7BDKPZP1V+$M1C&)>@5A)I7'6&! @%%PIE(BT(WPDIE1/1:0$BAF]>,!
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MJK/!U$$8Y9W>*#].EN'6^+'?%4+KVQ&A]?M%:'WFZK7@P5X]_NG9^6M@H0=
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MR)W\!TQGS+<&YG%'"G.D)S[[%W&9]B?"'$>M8M.I^E!D[SC 7_X+4$L#!!0
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M]#[SR ]Z>8=MU;R)GR%-4F&57Q_A8HD)("A:WRR6K&08=E#=O8P^S'E8+1:
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M3910T?F*"%O3[&*%2E2?26QSO9=_\MLMCF>/D"PF3Q&:90O35Z]!M.+[SAA
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M^7;XKS"93%G2WQPYM>'>C*?<N(=K#7K\=W-#K8W(6X5S 3[N$PM#Q&T$T1U
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M9,A"_MCC9=;F7;%#[H 0]X$I=NI94&[V1:@I!U[LD^AVS<(+FL79@9Q@_4A
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M2]9H)3G>_92".)@9GG (!>3(FOSZ"W#(&9)X:Y# $!Q/G9Q$$AN-;O0#H-$
M&O_XSY=E\NH9TRPFZ:^O3WYX]_H53B,RC=/YKZ]7V1N417'\^C__X__^GW_\
MOS=O/N$44Y3CZ:O']:L/EY_.[F9QPDBS5[=W$_8C?O73#^_X_UZ=4X*F-)[.
M\9LWO#"C^O,7_J]'E.%7K-(T^^4EBW]]O<CSIU_>OOWV[=L/W][_0.C\[>F[
M=R=O_^?S]7VTP$OT)DZS'*41?OV*T?^2%7^\)A'*"XEKQ5\>:5(Q>/]V6Y>2
M@O_VIB)[P__TYN3TS?N3'UZRZ>M21/X94$E%_B+0ESJ=_/SSSV^+KUM2QBC6
ML*ZI7=#G)UOB.N&/Q6_3_#5KY%>O-LU,28+O\.P5_^^7NZMM.=9@<?:T0'2)
M?HC(\BW__O:"I,S\>?R8X$O\F%_B',5)QFHM6.7K)_SKZRQ>/B6X^MN"XMFO
MKQFSC#7:Z>F[]YLF^Q<5I[?=14L2]$@8X.)G?$8I2N=XB=,\.TNGUW&$TXQ!
M[VQ.\>:OO43O5E-GU:Y8'UOB!_2"^X@MX])9I(\HIK^C9(4_8Y2M:.\VU?/K
MT7+/.,L+9K4?'_#RB9F/QLGZ:OG$:L;37NUJ6X<+=>Y7RR6BZ\FL]C<W2F@Y
MNQ"==?V<HBC_C/(5C7-6T]DSXX[84# C-$,)OL<1_Q+WQ'N_&CNK>A_/TW@6
M1RC-SZ*(K-*<C0>W)(DCQOX^)U$Q"TPOR/*)C17%U/3AA?^(>VCKH%)/"N,Y
MM\%5REIZ6=3K34MU37Y4<S<;=JK&CU+G*(LC-I-=QLF*^6XW.+\F67:+Z3WC
MX@VAP%K]J'S-YIQ>0XT-=S\J\,$NS0E=\TG4:R_3U.2IEZ%LP?__X:]5_,R&
MZHVCY6;:<U2Q'\4O\0Q3YC?<8=;B*V]=3U6-MS&SF(JS.QQAUJS%H.9MW%16
MY4>YL@E9?811^>R%FIIZK* :\\P#;S 7:[N*T;Z6=GT$[U21VU54=_&U[%QX
M[MU%DS#QTP6[BPABZT?HZK_.Q=XQ[BPX]\RRR>R6XHQ9KYCP^XBK9>=JZ'(P
M:.UON-K#0.4F]M0SZ.1ZG'0V0KH9&WN.BKZ&%N=#BMNAQ-$0TF_HF/(PR)3]
MD#$=IWS'XIZQW8!C,N-+@(\)^=;5%0)S]Z="$?]9D&2*:<97,_G:BRZR:CS:
MA2R?*%[PL>X9\VB!'_N(M?A3:?+$-\RXE%YTJ;-WJ\0Y2OCVT_T"XSR[1935
MM\ Y&T$29XKHJO"HC!_Y>XA\2:(5MR>;Z3^P@3E?U^*=7835\ZN+B6A425K^
M6!=VN\\8I_G;:;Q\6]*\10D !(J=S6K#DF^X_EB(6W!S(!7[F?=IDKZ9XAE:
M)0"?$2RCA+=;B<D2Q0!C=Q&X9.U"WH+5FR5>/F+J4M@F7P>2+IA0-%H]XC?;
MAG HKY1[76H&DG@3P[EFOS8JQB\Y9F/)M*J:B]MG>/!6+6#(*ZJN*D](U*@Q
MX6<T"!6;.*L,-T/98]'(J^S-'*$GUMBG)V]QDF?57_BX=O+FW4EY*N-?RC__
ML9T"F9[XBOVX'=39&@HGO[Y6$[ &Y)K+"-X.IL]9EK'V/'O,BNAF2Q?YQU*/
M]L>F#CM G-&F-JRC5)S*/M.Q^\\H66K;FQ@TV,GXRRN1S:N<O&H7)Y2YH^5A
MI>%L=AVCQS@I-IA9SQ0=984U;8N5K00O%B0".FIMQ@:<<8F:TV!0<[&BW.4U
MXT1!*")#( P="WK-K*POL"KM_7Y8>U<[5E_C?'&QRG*RQ+22>GU#TF@C=LOX
MEJ7*]@*7"A(6W70V8P3,MP3,OPX.F'K06@<1/=T.%"JZ4&$ T@MD>!6GTM0_
M=C2UN.3F?_GCFJ3S!TR7D\<DGF^B,A]>HF3%#U-#S=J+1S4C=.,1)!Q<M =@
M'NE62PFC?QO8I2B%OR8HS3ZR-CU'Q3%S&:RD-"W8M&B"AH5.'[C96UQ*L_Y[
M,)ZBVC54^X*A&DXINY6WMS723\,:";SL R]Y1K>T<[B8 RS??@ZF4TJ7FY:+
M?<M%?J (L-2R_Z)^%P)Z-[2SOER2M!"P.(,@^.CRSUO7O/TY2/,:M( XXFT&
ME?D&#N&=3:>%X"BY1?'T*KU 3W&.DIJ\[5 LN$ 5G@44"-+HUIH"PK@ EA4P
M!H[2G471:KE*^([')%]@VC@RL#D Q0\.W.!\,GM +VV4="M=0<:V=)CXZ=4&
M ##9\J^0-7 \\(Z?Z4[Q] .B*;\X7=/CDBD=Q6W'$5Z@;#M(@2 A8ZVI&240
MEA4P!H[[&7U)HU\U&G_1@8>H\PF[1O7<S1W\?&5VB];\A/F%-,RG)]K-!%*B
M((T*T@@TKDO95,8=.-;V8?F4D#7&=[@81,3]IY:=P?1E P'H@[2^K9YF(  X
M5I@8.%#'($M7 "P8Z7;=7D47I.VA>H$ZOXI39>N!XWVEA+4[$%I;J^F:MI;1
MA6QKHUY@6\LX5;;N&NOKOSTG-VIW!O8;<V'#H'=+.-V2:P/G=/"HH.;$@1Q:
M-D4@ISW"AD\';7N>\Q @$L[A0<588YI-1^,>./ +- [!Z="1PN)LJOXHGY:F
M<8YW' ?X(/I 3_6JCNV=#ARGNZ7DB4TQZ]L$;4[>_[6*G[@.-[AM7@AIV2IZ
MTB"-;:&=V>9Z9I7I!X[$?>1*X.OXF7NG.4KGW,_8H%4T/HRX;" 3<9  L-+0
M# $3NPH$ T?QBDV%4BS563TM3=D@"IH@+0W1QVQ@!9?*K@,'\#:"22=HZ8P<
MJ*FD$D/GW)TQ!HZ<\9OR;!9H9^3*+Q"E:[;.DYZIL"E3+95@98*T=!=] 8LE
M&-<*)T-'W:K4GA\)O6^E]GS,=[\I8G'=2E?#@&WI(%'4KPT  XLM_PI9 Y_G
MDP4-BD&2^2+P2(VBA"90(Y0($C7VNG8+TP@\J[M; P?RMHDQ1;]?]JEL@^:G
M( VKD=YLP6;ARE0#!]1J7J>\WZH)1$\][%YIU,3*1Q?Z7$@!-5T@31= "]1R
M_8RFL-? @;*MK$4^Q9;!Y!_;*1C*CSY-5LM8 SNAI)$;<CJI6;PR51'8RD]^
MB1*2X>FOKW/*G6S^!S8IXI?\0U*4^O5UMLE[/J1=N=]VE69,Q"+WR$O<7C2K
M"<IVDA'XM+$FYTO+YDVK$H N4IL7;+B]9<7#2%+1E.P&+?%E(].0U)8BF=2B
M=3*OPZTB2]+&J!K3"895*E8WK\A0-'&=T4$8^H_3T$S=3.'5Q]:";MVMS5GU
MS".B.)Q2.])PC].8T!N2X^S=+1O1F 2?&ZZ&F ' 6$1,!J I,I#O9.RKI)/.
M:FOOJFBE"]"P[MG;[:Q_<OIC!P"H2NDQ()8:'PP,FO=$@LA=' K^\;;56,PO
M_'.X#&W-I)K#KQ$$9WN<Z=J.J;\LUE+AI/X*RD6[8BL^BK/\CJE6Z#<M!Q<T
M;Z^B[0M*G3A]P2"QTUES,WIL6(>1.NZ8:V+/N28&3QVWO1C-YO$)W>"RV)FM
M7E$3'$)P"3$%@;I$D%"PU]4J48&:9RAIXK:B%G)E9ZM\06C\]\Z!%$&AHA3!
M(%*&#@*#;E;&%WGU3!CGR^A76;8R&[Q)I3)V134.0TMUZF#DBD\8J=P$\2:K
MG#\#SB^]F*PL(569ND$Z#GNKM>M@] :S,+*]';?1P-MH/QUWT8Z[:&/:7 EM
M:^6XBW;<13ONHAUWT8Z[:,==M.,NFLT;>\,O#P0_>YP[:.5CYZHGCU2?MRGN
MVI^#7,0:M("DKVLS",--NB!9\2[QAY<GWG-45C21;8=2%5F05@5J!0E+J!B%
ML=]4CGOI?)=.LV5@#45UJ%Y&$:19S;H CM7+>(2QF71#4M*4KH2=HN^"Z<O&
M = ':79;/<T@ ' ,8PMI!U+^] 6_EQ6G*R;TSM\YQS-"<2U%UX<7I@&3/DX1
M71<:\RO>_$8729)"W\TV>@M,>ZAI>_?*8TU! GA_;0NY&>91EC"VX+:BEYWZ
M'*>L6>2 5U(UP"JA"AAH)IV@()'P"6,+[@;G2G]'^JV: )O?@C2A3G[ Q-8L
M'<:^6979NSJ?<8ZR.&J934M3)=Z5TP1I1H@^@ 2[<BYAO*O4%NXR3E:Y<-+!
M0*4P[99J%,:5ZV1OWBV?,!Y2^HKC^8+)<_;,7(,YOEGQ=IK,A/UY67_N5+9L
M.,NR04*DC_YFX%AR#^0E)H74)>I-AVDZEM9C2EUZ3*@"MD%G7*GY!_)(%$]W
MD>6;0^+<^Y'G E%0U%*""!1!HL"L"RQ!B, CD)>=JO5DN?@0+"G]NK5BZVN@
M%M3I +%>JWP@+R=]8LW!5QZ3=(>O]@)-2U.V@((F2%M"]#%;5,$ED(>/BEPT
MRJ!I>\<!1%S/Z*,A#M+D5AH",_UHV 7R:!+?"YO,/A$R+>[R8?H<1SB[)XEX
MN-U$6-M55!$&:7BP9K"=116KO@\I*<[>W.$,LR987.)GG) BIS.K^I9)ERKF
M6HL2VVU_0(D@;6NO*^1P (!G($\DW>,BF/\)IVP42IB89],E4X_OA^7QLV*L
MMRM4'7,!%@H2)ITT!IRC![(-Y(VE]KD(PZD2PVF20$UMT,+^]$C_9Y/<'NVJ
M=@#;N3ZWC_CP=';LGZGX?FX/#LT#8G8<@L1)_[8 'S.SJR.0MY:.]Z; ]Z8V
M;QX-<W$JHWG-INRWMCW9G_B;*]-5E$]HZ;%*KDOI2'9OK$A( KTR!=!'?VE*
MSL#+,5$;&];7'=(K-$:ZIC5E=,/=EM):C<"5JYM6QK-F8!FO$5M9N$TTO)UE
M5Z4Z&UI[6\K:U#XO3"W9#!_%*%'<C9%_KETL;WX>R(<R=SAB5$9B(9%?=9V\
MR<?/=:9J@<^$J*WQ2V=-:BZ+$JV0BK9$R$:U5QEL9Q!K7]TR828EF_7YV9QB
M;#*]18EMYP64&,CT-E8E792O@P!0V:;; RKQ,Q)\>$JXATXSG/X78<T(' YL
MBU7GI<#%QH&.CLW0 2+PFOP,&_=/<4K1W^B.K%'"\R)*86&@JI;'*JJ!C*Z<
MO0E4H[I!V]R*9;.*2QB7[LJY2FI2Z;>F9QVP^732FXS6*NNG7UTSQX"M$M(Y
MZ__%AJJ^@T')M_E=3>0!VLQ21Y,9S>S$:W1AW1)G6CU1O.!:/#?N  PAC)C<
M\GAUW>$-((I1AB_QYK]7J=C:=\Q7_$CH-T3;YQ<ZEM[=&+(K'>2>1K\V -TP
MLN,?Q@0O"LD4V>R\W!):6"W/:?RXRGGP]X& KEZZ9:K,&]R-:9#H]-)B7?(1
M=ZLVC-P!FO2DFOR=(TA$VBO[J#3EZ-") 8[W':WN.X9P6K;A:VYDW#[ .R,T
M:SS >S;]YVISYI<I-)D]H!?I>+)Y*J0%@#W55C^OZ[.V($&ZWS8&GACV*4\8
M%_E5:C*G$,?S=//,9K1^H"C-4%1HDTZ+WY(BE4%UJ/Z,QGS=>LG:@LW4F,9D
M6K4"L#-YJ-'0H9S6.*I.Y:^MNW<LIS*%D42A<&8W?DY=S.(EA>JR.8]>+/G9
MQ8UR5'0_>G*I+U:Z< D2V&[:!+@<Z5)/&&DA%.)O''"Y_##P03CH@:?G,";0
M6;1%9\#IZP@C6<7._\D>R-ET6NB)DEL43Z_2"_04YR@I-'AL:W"'V4H_BW-<
MGC[8Z'R'(S+?M%;1WUK(W%=UU</JWJL+$O-[;F7 \^_>!0HC,TA-SSN<\)V-
M!\)<&WXBG8?'V,C '";0$.Z D]@'[#F%#N^>;6.%7/NZ LDOLIF'>&=CLG:#
M8Q\6C0"I+8L@ >B@-: !5]M* DD\<KS: K[:LLDJ,I(W@;8Z;+9Y./9(R@='
MR7T7$&W;ZG+:0&_ V&BHOPICX!3&)F]+-NFM"2U-=4A33C/<G1B8'0E,.ZFA
M98R+4Y=RAB.WMW"#9%B+RV[']#.Y]HI,-Z,[N"?C_B%'Y<4:Z7?QR<:!#P'J
MNRLQJU(WJY19ZXG&L$[=*A;:4J.":+<K2BUMJ,:V41%D> /#,'KS612MEJMB
MY:K:Q)$#PK9<!0YXN6"!TE%U&&C@S,,X9'.'<R8ZGE9)>16W]W1$VPM[<J)0
M<0!2"F1T%2?Q7$Y@!\-1MOB8D&\^#X3S7+RLJEN*,U9I(^SCH;;[>)[&LSA"
M:<YZ(EGQ9Q[FMTSW*,8^M93D:_10RT<4TR(@_AFC;$6Q[_IJCV%XO3)0O[U(
M*4KG&\W.TNGN\D5UJ]'SY87J74#^?.!^>\4>4*KM'4/77P1+]M1'O=<E[:G>
M:[7L27N0I]&?ROI\/*I:/.!Y&6<\R,J:^UIQG\>BA/B8JKK$D(MYL84?F*'.
M6:5_JI57TXIJRV@'N_4'-Q^Q4[AY"]!83>L561E[[P\)MV23;<4 J8U8'V*S
MIKNQ :KV,[>\@GI 8"3[/>KWUJ7/R4OV/60$@V[G0'$@O"=OV-0Q\!4?E0]I
M:\?TY+;4VI*7N64VKY,-M\>CL:5@::5B=7N+#$43UQD=A*&%C8_!32W;W.EF
M:^VFCIVU?28]D[Y,+WWT7ISCC47$B5Y39" GS]A722>=U=;>5=&:YC6LO3MW
M];I/3G_L  !5*3T&Q%+C@X%!\YY($+F+0\%>P[S:J$J9W*EVHO:2!ZN3+LMP
M5W-4G*'YG.)Y$?::S$H156MV*'DU8QG)@\T_KGCOW+(4+,_XX&^?@\UJSC0.
M> _=5!L@U[CP1OK KMXQF?U@@+-,;>\ ?/I$]VZ]D"]/K,'2_!:M-]D!(QP_
M"ZDR]$1E(ZB(1H  D'ZV1E8Q[7D20&%' Z1JEWEO*4_U7!YW:<^_?=G A@H-
MFQ&@Q5$;.1XT--7VS!BB0%SU<.H#HG.<9V?39Y1&PM!AH*J2N*BH1@ 'F(:V
MUE9R[9FUPF#,W7YA@:W=%B-#%:)Y*JQ'[0NV3 XI."(46+=#5V! *NJ9A,&
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M26[1NM"*+>HP^W7:QJ>1L *AAO#0D 9M$Z]PT@@11K#N#C_C=(4_,ELPSZ&
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MW.B/UX"RC'[(QI!EM@WZVG9Y], -I)UN]NN;,R]/DS3<Y7=I6L<R^*]A.,Q
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MN@EH3Y6@M,0IHSZ@K7-])YH"1+X2;=;G7N03 NF^$8BI=C4':4^)+CCF]BQ
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MW8+<O9!CMMNQB!QO@R3A#TJNMOO\%*S;;ZSXD'RFZ0-;>_2(/A KIE(E[5%
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M1Y\BJJ@.\8(LW^HD0\%2RS-IKK\YX&C%=CAR/!#3\^*EK\DJ#A_YOAG99DR
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MA$Z^A8?<Q:O*CAHW-7'Y>* 5=D$Z@?-CX-NA.<'KX*2)WEJS)U^]V=;S6@5
M-9QY90KP>@=2BJU'J#$QADQH6YA06H%YTP2S0<XTM;M32CH"\F:["BYVL030
MO/4*)3R:TFFW<$VI;GQ77KYTIWAOJ]J@TAV)P5@1Z87$GRZI4F@Y+G<JMS96
MK[CQXFZ+NM<8]'<6Z-.S[7!!$<D)$/#&WLKP]B@XK&!07/'DG:UC<* :/ X
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M@D$S->1<VHD>6BXG@W>DUDTTS<1MK?WL 3._(+'\?A-?M9]_Q\(DC#'.6!P
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M+TOM3/35W_,UB(:?XU%=:V=7#+<WW(NW6W(UJO*^M3ON7JG1%*-0+^3H[8Q
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MWN<W?8\\G2=].ZS[B5:A66^90[-9PC#0?(P<N-+N8;]9L*"&E\;OLI]4^\X
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M^9!X3*F14TU4;(6(SH'#HOLI#C+(%G2/2%9^\DN)C98S,4L63R(J=N9X=Y6
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MON1Q\6<_X.U7?UW3\"XM<7P3WU.7^D^T7@1)LU?V")1[F;B(HA)T[JNG5^I
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MWU-1B^>L$O:7>UW:;_KCJUU4JW)".[#&9HA=^FP2117=>."6TL9&>$]E5_O
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M)\(T>G;P.09-YVEUTFVJBS@'4\;><6S?H=B@T*WM5;2F\[#=T?+/FFZT0-K
M;=W&D>($;",O^7Y91;E6&UGL2;E=IH<(16=$+=:<@@@NHE]9%#'=H&_5.,P]
M_M8-'2F6S%1)QRD0X&+RE04"W .,?4W-KR*SFO$I*3'-]CJ4C!)T6VV:3I:G
M8B9^M.W66KI0\6UF=FJ.8QR'E6&*%();]9F'7X6?,\UH,'(6IV3?"'$ )WOK
MCB6G((&#WE<2)<;*U#H-FT*6IF3D"+%BID0:WOEA2AGB]R>GQ\'B*W'Z:65E
M=VGE5H?CYT[L$:]?$V!1 U8^UJ1AU+AZ;-#T,C&IC?9"JD1E*9S&=,L=)J%Y
M06%HFIU=B-]&'M;B+6BAMAV>R&'V6!E>C)7]D DZ_T02+[EQ0[L]=LI5TD(R
M-:=08 K6%Q\+QLZPFJV:4GHEMW#HB%!)K!H(P,F=3>'VXMW94NZ4&U RCW%;
M;I<?_8BZ7%YSL<Z^_8_R'N7^.+%,49W%G$7/ H5 I"/PZIZZ_M;G;<X@TC@
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M4M)TQ[EA],C*!AHF2YT2M9.D%HG#A#NI 2,F15TV(42W=A6O(@G:PD\$=;5
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MT7>V5"MK\IU-+=,ACD;0<JV:_HV^1R3"\ZMD/GS#VU79:OQC%I 1H-*MK+\
MP[=:HZG4V$?I9A60=?!#B-<%]PN<T*DKBYYC=(F>LTN4!5&<JIM,F:6T21\^
MO/M8F/M_$7'JT;0X#IXQG2RC%W1&2) LT1HE67I&(1:%*$GIM'FV)*CX:Z^F
MF]5D+-H-]0_6Z"EX17V:S>-BW*3K("*_!/$6?49!NB6]=2KGUT-S+RC-<F:U
M'Y_0>D.[CT3Q[F:]H36C>2^]ZM9A0YS'[7H=D-UL4?N;'2&DG&TTG0[]C 1A
M]CG(MB3*:$UG+Y1[0$W! I,TB-$C"MF7J"?>^]5H+.ICM$RB110&2786AGB;
M9-0>W.,X"BG[QPR'N0<[O\#K#;45N5M]]<I^1#VDM5#I0 *C)>N#FX1J>IW7
M.YB4XIJ&$<W>;&A4S3!"G0=I%-*9[#**MZ5+C-.4NCN/E,M@" 76.HS(MW3.
MZ65J=+@/(P(S=DF&R8Y-HH..,DE- XVR(%VQ_U_]L8U>J*DN'"T[TYZEBH<1
M_!(M$*%^PP.B&M\.-O1$U0QF,_.I.'U (:)JS8W:8'936-4PPI4JI/5A2C7D
M*)349&MQ]\049F-M5S$::VG7I^%&%=E=19DW7\K.AN=NWC0.DV&&H'D306R'
M:73U7^O-/C V;CCSS-+9XIZ@E/9>/N'W::Z4G2W39<%HC6>N1C!4=F)//8-.
MMNVD-0MIQS;VM(I#F1;K)L6N*;%D0OJ9CCD+@\SI#RF5<<[BY(^4;0&.V8(M
M :YC_-74%0)S'TZ$//ZSPO$<D92M9K+=(++PJAFP7_!Z0]"*V;H7Q*(%P_1/
MMY;A1)IMV&8_:^4@LM39VQ7B/(C9UOGC"J$LO0\(K6^%,FI! -M90$%D50PH
MS##M[]'D2QQN67_2F?Z*&N9L5XMWFC16SJ_>S$W-X-[2/S0J0Z\9HE+/J^I8
M6WL(DE=;51SCL%%7S ZC8-+=%4UI7?F6:(K"'Y;XY>T<16^IM.__^ O[\?OB
MQUQL^NMO%YAZ?&?/:1XEJ+C%;(OTG]]QO]%6,JE:W]Z.TMA*74^4:ZNMO$]E
M4YN?FBVM]^<9:;8Z(&'%B?[8Z,SNR9F2XNTF'Y7?AZLHWN-@0?!:I$TL;7J]
M>7]_T^#P)L-OFB4QH9/./[][QXY3T8)%1.NV4(^PW7FCX_J6^-"=>$9;/&>M
MOHZ#9:L7N=]*7;2^N=>/LL8K.K)5M.S)]X[W9 6__]H&)$,DWCV@#29M*Z*@
M:@W2#I5[_0P3"#AT.TS*OO_@2=_OCS!=T@E>T/-<FE:_MVC<[769,, ^;[$H
M>_RCXSU^L25,:==12OW-_T8!X7>ZBJSR'X1D[G4]4"1%[XNYE #XB^, J.![
MD.":_B45#'H!56O8=ZC<ZWV80,"AWV%2]OV/7O5]8<#4O<^AX_9_@\YU!(B%
MTL) @TV)@K]Z@H(G$B1ION,J]?A$9.UU68?,70@H1(*NUSI<2@#\J^, *((4
MUU&,[K;K9T1:'2_Z7&JG^]F]CE:(H.C@;NFR8__F1<<^H&7$A$FRNV#==NQD
M)(T.;I.XVLE244 =W>90=O9/7G3V!6)'@^*;9(Y>_Q/MN+TMH&ET=X?&U?Z6
M"P/J\ Z+*E+C>M"MBBZ'F&QPL0&2[XI<L)U-LKO <_YP!Y5HP$%1PE5PZ @*
M@HJ"804<UV-\A3!/P>O-G(J<[X@S@233OX*V 18AK:LP@0D' HB0504-UT.
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M%]H[-\G^B:*S,(M>BHUWP3L^Q@P.)Y*T&9S.71F_H&#>75I'K_3K.<)\1HU
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MUN8\I*XD]^XDS%V+V=&5Z!H1MG6CQ@> ='^ 44;J"T;@\AJA1,K>\^L_H'D
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MB:9]#(/SQ1?%Q('4TFG>B6AYT;3+* UCG&X)$OAN*K*&H#PR>_NV11TS"L:
MN8BY5J\)0@\4B\4+9]RV0PHTI) 7F-@:2'H"&TC,LP3=*I@9@+#V/:3.DW&?
MP:5\+B^]W/+=?G@Q"=KXQ;S#'$#Z?LCC5^#Y"0+HW(+!9ADRT3<">6*^GCNP
M0%]*;WK7\J.4K(\]Y >/CN@$_J1<CS+\=QZD44@=\<LHWF9H?H<R=OV%SL&/
ME,LI:>18<M;2PP8DH8W;=T'>0><[=MH-)Q=QD*I>EM4KWWU'%EI^.F5=HN=,
MFE)+3%"*RR-P11[V% DW-*@BX\I6)[-YZC5YH<OXB +A$241)G<X0^F[]Q]^
M+!/S"P[ :I4Z)/.$E9ILQE)V##:5O3EWB>HI\T7"^+MW@)K7\/?Z..(7D8*H
M7<1#!$FE[@N?-G/7T@<(0&]@@PP,D/_8D4K=V_3PL6/UE--D6FYO40"G9IE.
MJVT(,2M_]Q[,O=..;G6>'8/5U56Z][L07,E%FQ PXNI),06Q8S(+%HL@6IG$
M+BP9N0V#" H1<,J7CT"=@V'"-6V#E'7^7 Z?I<>FH&G9;A(ZF:(T>P@R]$BU
M@N:'A]2DJTU(0>[Z4U[0?9 9JT$3>3KU>+XS 9QP1",<]J:9M [A4#^RQ\ST
MG2TM9\""XZ6J[]BW,?K&;<W2O(#K.LHMC]IZE5G=TQ[')*X(;Q=#0L%U+DX[
M$:>=B%,(T+<0H.-;#Z==+']VL7Q= IVBR=:4US=>S.%VA!'AICBB4+""BCNM
M.Q'\O<7)DB5^94W+US$;G-"VI>7]S;-D?H>3L/PEIB8@H;W_(CRF;H=;=3*W
M+S=74',*'E;'/RWAPUYXL6>+# .0WA[-%\MZM5B@D*G& -J2LDIT<\L>-\#5
MZAH1X]S&')63R0VPVYWI9(Y5(_;>NUK/[P]H>;"PZ#O(C?V& NOJ4*).Z)S+
M[2B#XX]H6=C&!::%3OG/Q[P#4*C^ 6TP86T[7)R:+:[R-YW2XEN0AT>6LF?_
MK/"J[@;TXS6=0JMWA/:W_:K&M92EI&N]#,6AFVZWUTI'8[@26IN^?:JOO_7$
MJ=;?"!5P[]?B&-7:!^Y7KTW?R[&Y+\/A[\]!BO+WQ5"2YK5>O;(?3U?A1IL&
M]\<4JK,)S?XX(R1(EBA'Y?GN0%->WC[[&I"Y_(J<);Z=JW.]^4ZG]*(5_*Q<
MW&\5A)K?)D2-L>X/(B1SEI9&N.L]9!45E@:I8L(SRNM-C'<(Y99UEE^FYNZI
M*NFJL\IB.GO;PET%'_1?U)E^HG]@,5$28?*$_R-(M@'9O6>LN.)9Y-@!2@^.
MTYT 578W'D)IK2.BHD;D/I*-RET[[P 7:I;4Y:$FY6F%" H6M%T] 0[FK UT
M .=C ;RN$@<!/J 1YD'&%T2>\?2!VD&G? R?]UJ+[@%:E1_&%K?&]QV_AFAJ
M%T3M?$QN4D:%IBN@G/PBNB4X/B"ZSHY":D5SL;XD498^/'[A A-$6W:)@O9H
MP:JCHW%@JVB1[V]^W".2;Q E(<JUPW_Q4$%5); 641TM7&%Z&0>HPK9X_N8]
M/VJ%1PGCM*+Q]98T?6R;+?!WN\1^9!;+HY:BBXL]JV=]VZK6XR/#Q3(O/_VW
M33EA8>'W4LF<[XX(PXWN2BAX MF_R21;>9]CBJK9XC(B**3\M&,PTO* 2(N@
M_&060]99BD@*1!5-^\"I3!4I$53B^RI:)G*U3M/&)K\@ )3M@CZB42I\;QBV
MN3NV;$Y)5L,>_:V-._JGWZY>4;AEIS]GBT44"N+/<J(J?B,@<A4W(*% &!%Q
M\CPGF]@#P9#Y7**ZRE/G,CDYVDBHZ'&=;4[5EL\UCSF[_H)2=A:'XVISOI3*
M;7R9O.E<QYK[K=G\Z0\J","8HXV"C()VEJA<&W!)^6$/?LG); :_^\1Q%(#@
M38O0J$ 2'N$S/AZ76B3LTU=L"+Q.23#P:B5]!)Y(\-[ JS'V>*(!R$GK,S5W
MG+)PW-7+>HD\H?#]L5=G;>ZY3^V#\GP9+/<2N*JK7/16P9-SCCAJ'=<M;U1J
M&:E#AQL>F)@<%[SS]VK'_?#W"1K*/S#0_5)O;(\#LSV:^SE*HO5VS6TP]UO9
MY-:WR48G3ZE8WO3F"*LQ8&.D5="=?2)8;P:OXM[D?:MZL_G-N=Z4-%W>F\V"
M_EZN[IHY+#,H'*54\W*CT&E61AV%CCLGUZHT/]CAZLJEMO$FT,.M(..5/8;0
M&SP AA[J]SJ(R"]!O$5G:;I=%^?$SY+Y9Y2M\!S'>+D3750?K\:^/:13XY%T
MX4.4_L[>9:ZGRAFR V7U#=%]_/K</7=H<3! 3L)9[CK- XW]A04=MNLOY)'&
MH,U4Q*[+LV//E]%+-$?)?&B3(:MO")/!K^]D,H;I.O]-!E](QT[B3&LR?D71
M<D55=/:"2+!$O^"8<HNC;#>T[0!5/(01451\LB8#=Z;_9D4AK>_WBW)%/*MU
M]:QC@EG*R?<\>S)H177[,5!%WY2]&*.SIK,/ TDWQ&4N+^P!U4-$<N)[1"(\
MMS7\17S[CO8NW]/@[M<5?HWEKC#ET/V+IX>T+4;8;7N,H'"Q)?C<UO-?CR+%
M-QN5.IO/(T8:Q)]00KWC^)#@4I@N=XRZ^BXD875Y.$?G_RH/#3VP94TJ?'UA
MT#KZSMWR.ORSP%K@[C.#:W2.)7,,$:W7/"X7R=W,<)IZK-(WU[)(%'Z+M8UV
M=0U][:JLAF]DT [:,5,,6=L"?;/Q^KH=*[3!C:!99MW;5>*Q/HWE'EWARR#F
M2C)9-'RHZ39/)_9I&Q3W7^=/F$EL>\:55F)KTA54<AJK5KK'EU&KD&FRZ+7M
M\7M8 PP\AL$5]1W'@(I.8]E:-_DRG@%R#1'6]L*CKF?13F_*,']K.S__>!ED
M:!_PM648^M7>UUJ8UGXR(<-VJ"]VQ538TMC\Z.'](S>VSPSV.9S:.(.UW_<H
MSSY7.B(O49G/MZ.M.YR\T!D8%4OE] EG05S_?H'3[ YG_XVR!Q3B91+]24GY
MVV:CU=?.P#]<?4?8>;7G'-I1^5'K'+H3FW5._];+X(,"3].!@M=DAA*W\0C$
ML&+Z?F1B.#7M.16%9MD*D:=5D(QM5H#M&-S4*-MQ,C]C=O11F22EZ"<W5:"Z
M8CUXC4GY)T;7WJZ<IO*A#9*@\I,5&KQ+C\GT".3U/$VTW1#*V&O>(<(H(\C@
M;X+"03+^6,3@X*F";+35?'=GZNX_"T.\3?+C(SB.PD@0KA_H,?G6RU'"MN3]
M9*\-[J2?T]^'VVL!9-7.XKPQ]*?9HCWQ,8N6-GJEVFT;LHYJ3VV8.J;KF)LD
MQ.L\-W\.P=NRN9S<F@#*4DE22N=$Y:;#!]'*Q9T^73Y#&#4[02QX^%'XO12,
M\WTR@P_K$*P6JFF[I6R9^>:P<^U:P ,5B"IP=8E>4(PW^:R1T/DCHS^P"\9)
M*NA__8*'!VS!!=U'C+$:-*&D4\\P;[*/.N.CF#)=EANY5-"S^3I*(N88L3>.
MI, T*EO-T'IEW8=G'V5H(E2S*O/5HPRDT_=!.[.NCC, TGB5?5?!^!CR\0[A
MBHN[1"-;K\6&2;K2^_=E[:BI$Q_1"?/K<]>)X^MP=^X<J]8]>:V+[@X<M2E[
MIK[75F]B.1NU9-<K5.H 6LBUX#@GY&4D/RAZ78MI02LQMWN.. A#V2=QK!FR
MO6"Y59)H\J!I2H[)'QEV(AO)A[$NA+\O;.CN+PP7<3;;:[#:'DO=^(^WG5ZD
M6/F]^,;]U.AA])JA9([V'=7H8UH@2C=4RG7P W7$B]IO\JW1?&?E B>YECX'
MV99$V6ZV.'L)HIC)M\ D#6*JJ9!]H1J]1!G]E'XW8:!ZWVZ!AR>AV >E.103
M^G*5MJ\Q>6QI^[GJ%<XHJ[PZP^*5?Z==W%YT%EKWKU&VBI)9@OX;!4286<D2
M-TV]"+E-9Y]- 8%MZ[!EGS7;E7O3?=OCVH8$6 D+6C^5YVE%\':Y>OJ*F63B
MM&+6^>J:!S7?HQX0NGH=;V@ 6C;9<5P;@X0*5(G&WI<]2^94V)^#>&%QP.C6
M83)XX'4<_T RU/?(@PK>2M?2]T#%S(],]AY" BZ:@Z3#Y:B'@5QGXP&]TXX>
MF6P8J\F@7'B(UOPH%3NC5<0WYS4!M3CV.D+B(XV?[46 ^_+!WG;PIHA0/;!C
ML^U[0QHEFH\=RTMX"5!]7?3'(*A.\SP?4\'L@S;,/FC#[,/1PJRMBS%@]F$/
ML[_Z [./VC#[J VSCT<+L[8NQH#9QSW,_M73K5'95H+.DA:R<<VI2VM!.LAV
M])3;4H_;]3H@N]FB]K?3]M.P(L5Q?E=?3TIU(8[@LD+VII5]0G02O009BG<_
MHSC?Y@T2.F9NDE]74;BZ2FC[=C\'Z=4?6_K#H4DMF>TP*W71EYD3-A'0\]BR
MWL1&4]P89D?[-F*8XUI6L+U]CJ/0$K3[\&HCVXR7C\"VH+7>N#9KPS!W:=QQ
MT8SF*9!C!N7L>T:N@U _XW@>)4ON_6(%5<<!:%%-)]YUE 1)& 7Q34)[;)M?
M/.O>[U50E>()J:83[XD$24HQQ][8*\Z[4:W/%IR6ID^T,2G_$_<:\!"L2T7:
M93V=]MD2[;!@XU[GDY&4VN"33'EUFFPPH4X40#P0[?Y*M91VLBE&VG2L)V-S
M:N$5*"Y62SGZ/J5\>?R$J?N0Y 9RB9*PC&8HL*1;K%0YO)BS"#.4' 8V.'/?
ML_9]>7PB*$BW9*=$FHIPCRTQH<-H DH'Q8^8W63G7JPA)K^UROP0=J<@B\(@
M?MP^SZ.7*&6+< %Z= KMD00KY#"J#*2&(@S&>K)'EBRA+5]$ B9")5VI70F=
MLS""R@9#CH2;YX_2#[+ZPJ#U2%/U-AO"NNPX7=XB\J88UW*BZN*^@,A>8+E=
M0Q5:I#T]1X?@(D@$4%F!9(JRTUU\EG<3[J>%UG5F;EWYA52].ER[!]-I?K$O
MHXDN:2$1K 2%?,(31&YC( F8#['Z.X()$V2TAYTR14WPO,=407<\: RZV66"
MMC#MVVV#OWFM5%M &+J-(MI^:[!EFA>R\SBGU$%<.IYQ,@_([H):XR4FT9^=
M-%Z=S3= F<Y6G+2,"XI@J9_Y;12DI]4MV#V>I"QH\27FO=EF=P\..1C*N\PS
M<HM2429([9+[/) :)1TP*.".Q'VT(MSV5]1>9(?4J'4*\Z2)OL^8H/S%GJ+]
M6OB3EE4@4%#V2# (T<P0*!34ZV\*(KT9#_>8%$3=(:FW=3I(6=]1NWPFO@G8
M 00RMXSS'EY02K*:!T1_:WL_]$_U]R#RA=UGE*WP_"!K]Z\(W05KQ/$,;;#J
MONY@P&I<#8K:PO478<2-8)*8V-[,?!Z%NS"F9AN18(.V612F]W'(G8@AI&7[
MY:03A\"4?8"U9.4%P$15,&LB9^U: /6>X#](O:UWOW#!H:0KM26A\P 64"EU
M,2'AZWETS<K4@#7-IS!9IW83#G%/<=5'[5A9G-K!_E:_.BT_J#?M(?A;0=9V
M *7P,/RM"]G4Q1=.KX.(_!+$6_2$S]:89"PA*DN%>AZDD7YR2BUNRFPJ0&[N
MJ+5YS*';9H4>H<4%BE,7=_ >O!YB./>S-94&O2,/:A?O+K>Z/3V<SG[)EL9!
M?1ANU]N8)<O_1'":?DD("F*F@D]T_CYGV8?14_"J-Q3T>,+&!Y3G-S!HC-0[
M]DB"-M+W ^VF:KBEO]D>7ER>/8=7B^>W/+QDZG5F>+4::>#P_U0,KP0M&7OG
M!E@S^\KA-[#7RR\&2A98+W:,(P&HI,'!+FZ'[_<+VN?$KE_N(J82Q2G+-IG@
M7.6![!C0"52"=32*ZYTL >6 Z&MZ9@ <\@M($-DN<*S8E"IF%)2V6S!9)LM1
M\,I<'2V\U@N \%H4.'Z\<A0S,EZ+%ABDQ'3,6^5)"< H )7'B\,ID-<G+^90
MV<1:2[R6X&?)'.@\]N;#37JBQ><8H&I+C=;QW*-A)>C_YLK+ 4:B< **-D:
MA&V? <%E^\V.#[62W1@NW':6H^<G5\X?V9",XT3;9FMQ]!R/0SZ0DIT</0WG
M_KW.3JHM[][F +(Q6FP,C6]X'#@)^@/"G7G$KYV9MI680)6;]B8)XRTM<)/D
M25PNMH0!XBQ-4=:>,T:H29#;V&I-QS"BQNL*Z^-NT*97H]-J)K1)#Z3>=HXU
M2O?T3([[J<ZE[IL@W\8#5GW4IX7AQU(-+E]Q6)IOE;JC3$5"<5FB:\T,XBU6
MENZK3?EX2^W')[1FR6Q)%.]NJ"V-J"RG9UR&%.F4I_V4I[VFDU.>]E.>]E.>
M]E.>]E.>]E.>=E]P=\K3?LK3?LK3?LK3[B;:3GG:3WG:ITX[^PWE:3^EG#VE
MG#VEG#TEMQCT/I]V_@KM%!4N!(GE9PLN<))%R19O6\=G[G$:Y5L$*$U9&LGW
M'SY3RE6ZWS$MO^N=Y;)6&^@<BX7:'-R?US_48EOKT&UX^ D7"RWT/? F5J-*
M.?^UI7]CO?&"+J,TC#%=[R-MVV:E%J5![%G+L5C108WFH#;229-H![O6[:BA
MV>PEC7U;Z[]I[:>/2@\S<HN3I6*3T!9S*V.WR_PT=@T[PI.QVY7"]WTAN3[X
M6M :H7(6H'$H8O'MCC:04AT94Z*V]M@?$UY== (#>HEY;*X+3!:.@[7,=\MH
MKIA:,B_V9^M+107_WHM$(7]7IRE=E[LEX*"K14%=@RP>.W4Y:!W[@MOZ*E+>
M0;8F48%8]I>3'7$,5I>.Y6"QZ[,/.?B!=0VR^CP-?NL=Y/S@5XICX(1Y-?A!
M^K:P7NTSD($<O\7A:J+LR0<EL-&],_4^?4O+7-B:9MP%KK!-0QSM]>GB\;!W
MBVU<'W94SZ[<(?;Z>=*I[Q#W/8\V^AWB_67]S_E=!52<5)SZOO"^58?@H2A4
M!B&M[J%*22>\:UNUJ\A><9;,;Z/@.8JCXJ1OWB_S6?+ K""AF*,$=YC.2N6O
M>5X%WN5CZWS;>NS/UP&EG^]JT+\FZ(\M2L(=[[(SO$1;4;(2#JB USCNW6:-
M$FT5R$JXI8)T#USN+1.=(A(E=(M,=PI?HU>QD0):)^W5]>5GOT'U>.X'ZA@5
M@>[E U"@>G%U(M5WJO'W'H/]B1&;3 ^"KNG;J$8'RAKC\1V*FGS['W^.$*%]
MO]K=HA<4RR=P0*'N'"XMY( NZG:RVU;PA*XL*YO5Q&4=4-!-LMEF:=YI[^5S
MNYBR+3R/<GK#IM6=6$=P]50NK+!AF'@5^7[8E2?<!S#0/H"!]N&X@,87? "@
M?6@!S=OS1SSA/H*!]A$,M(_'!32^X , [6,+:+[N!FAZ3*+%(="A$"Y5)'4+
M%XKB.D_K%M&Z!>X5C[-TD;;'\G;%*;GB*;GB4217_-;2$ Z5\<4\?:'MU"^G
MM(??5MK#H1!M)5VB;7"?TBP>69K%X=!KE)[1/EY/:1U;:#W&M([#H;AW.DC[
MB#ZED:P#VN<TDD/!UBS]I&VD'F_:RE,BQ%,@SB1UHMW(FR+9HH%?8SO4EI*L
M9O#I;VUC3__TVV.X0O-MC&:+XM&PSRA;X?GAZ&[WKPC=!6O$B<'98%5V7#]6
MXVI0U!9N3 Y&W'CM7DQL[SW$\RC<A3%ZHE-&L$%;ZM:D]W'(G?$AI&7[Y:23
M&21@'V M69NF1EX%LQ]RUN;6_@619SS BYGW!/]!ZJV]^X4+#R5=J2\)G0?
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M2P$"% ,4    " !GB:14(+Y]WF96  #5/0( "@              @ $
M97@Q,"TQ+FAT;5!+ 0(4 Q0    ( &>)I%1<>W!3$ D  !LT   *
M      "  8Y6  !E>#,Q7S$N:'1M4$L! A0#%     @ 9XFD5'.0Y*@]"0
ME#,   H              ( !QE\  &5X,S%?,BYH=&U02P$"% ,4    " !G
MB:148?]6H=P%  !!'   "@              @ $K:0  97@S,E\Q+FAT;5!+
M 0(4 Q0    ( &>)I%2['G>JYRH" +%(&0 +              "  2]O  !F
M;W)M,3!Q+FAT;5!+ 0(4 Q0    ( &>)I%1DPV^VP0\  "NH   1
M      "  3^: @!I;VYS+3(P,C(P,S,Q+GAS9%!+ 0(4 Q0    ( &>)I%1W
MZ9EFZQ   $#P   5              "  2^J @!I;VYS+3(P,C(P,S,Q7V-A
M;"YX;6Q02P$"% ,4    " !GB:14D$!#X2X[  #\X , %0
M@ %-NP( :6]N<RTR,#(R,#,S,5]D968N>&UL4$L! A0#%     @ 9XFD5+"]
M28# L@  -<$* !4              ( !KO8" &EO;G,M,C R,C S,S%?;&%B
M+GAM;%!+ 0(4 Q0    ( &>)I%3>1?Y%'E   ,J)!0 5              "
M :&I P!I;VYS+3(P,C(P,S,Q7W!R92YX;6Q02P4&      H "@!D @  \OD#
#

end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
